Peroxide formulations and methods and applicators for using the same

ABSTRACT

Embodiments are directed to a stable composition comprising stabilized hydrogen peroxide and 2-propanol and applicators configured to store, dispense, and apply such stable compositions. Such compositions may be used to treat skin conditions such as warts, condyloma accuminatum, molluscum contagiosum, acrochordons, seborrheic keratosis, or a combination thereof. Some embodiments also describe take home compositions, in office compositions, over-the-counter compositions, and kits for the use of such compositions.

CLAIM OF PRIORITY

The present application is a divisional application of and claimspriority to U.S. patent application Ser. No. 14/692,665, filed Apr. 21,2015 entitled “Peroxide Formulations and methods and Applicators forUsing the Same”, which claims the benefit of Provisional PatentApplication No. 62/085,466, filed Nov. 28, 2014, entitled “PeroxideFormulations and Methods and Applicators for Using the Same” and U.S.Provisional Patent Application No. 61/982,217, filed on Apr. 21, 2014,entitled “Peroxide Formulations and Methods Using the Same.” Theaforementioned applications are incorporated by reference herein intheir entirety and for all purposes.

BRIEF SUMMARY

Embodiments in this disclosure are directed to a composition comprisinghydrogen peroxide and an alcohol. In some embodiments, the hydrogenperoxide is stabilized hydrogen peroxide. In some embodiments, thehydrogen peroxide may be a standard grade, food grade, chemicalsynthesis grade, semiconductor grade, high-test hydrogen peroxide grade,antimicrobial grade, drinking water grade, pharmaceutical grade orcosmetic grade hydrogen peroxide. In some embodiments, the alcohol maybe selected from a primary alcohol, a secondary alcohol, a tertiaryalcohol, or a combination thereof. In some embodiments, the alcohol maybe selected from 2-propanol, methanol, butanol, 1-propanol, pentanol,hexanol, octanol, nonanol, decanol, 2-pentanol, 2-butanol, benzylalcohol, ethanol, an isomer thereof, or a combination thereof. In someembodiments, the hydrogen peroxide is in an amount up to about 50% ofthe composition. In some embodiments the alcohol is in a quantitysufficient to decrease the surface tension of the composition. In someembodiments, the alcohol is in an amount up to about 5% of thecomposition. In some embodiments, the composition is a solution. In someembodiments, the composition is a gel formulation. In some embodiments,the composition comprises two or more separate components that may beadmixed before, at, or near the time of use.

Some embodiments are directed to a topical composition comprising up toabout 50% hydrogen peroxide and up to 5% 2-propanol. In someembodiments, the hydrogen peroxide is a stabilized hydrogen peroxide. Insome embodiments, the topical composition further includes a stabilizer.The stabilizer may be selected from stannate, sodium pyrophosphate,organophosphonate, nitrate, phosphoric acid, colloidal silicate, anystabilizer known in the art, or a combination thereof. In someembodiments, the 2-propanol is in an amount sufficient to decrease thesurface tension while minimizing spread of the composition ontonon-targeted skin when applied to a targeted lesion. The composition maybe stable for at least two years at 5° C., at least one year at 30° C.,at least 6 months at 40° C., or a combination thereof.

In some embodiments, the topical composition comprises about 45%stabilized cosmetic-grade hydrogen peroxide and about 5% 2-propanol, andwherein the topical composition has a surface tension of about 42 mN·m−1to about 55 mN·m−1 at 37° C. In some embodiments, the topicalcomposition comprises about 40% stabilized cosmetic-grade hydrogenperoxide and about 5% 2-propanol, and wherein the topical compositionhas a surface tension of about 42 mN·m−1 to about 55 mN·m−1 at 37° C. Insome embodiments, the topical composition comprises about 32.5%stabilized cosmetic-grade hydrogen peroxide and about 5% 2-propanol, andwherein the topical composition has a surface tension of about 42 mN·m−1to about 55 mN·m−1 at 37° C. In some embodiments, the topicalcomposition comprises about 25% stabilized cosmetic-grade hydrogenperoxide and about 5% 2-propanol, and wherein the topical compositionhas a surface tension of about 42 mN·m−1 to about 55 mN·m−1 at 37° C.

Some embodiments are directed to a composition comprising hydrogenperoxide and a surface tension modifying agent. In some embodiments, thesurface tension modifying agent is an agent stable in compositionscomprising concentrations of hydrogen peroxide disclosed in embodimentsherein. In some embodiments, the surface tension modifying agent is in aquantity sufficient to enhance the therapeutic efficacy of thecomposition. In some embodiments, the surface tension modifying agent isin a quantity sufficient to modify the surface tension while maintainingstability of the composition sufficient for use as a commercially viableformulation. In some embodiments, the surface tension modifying agent isan alcohol. In some embodiments, the surface tension modifying agent is2-propanol.

Embodiments herein also describe a method of treating a skin conditioncomprising administering a composition having up to about 50% hydrogenperoxide and an alcohol to a subject in need thereof. The skin conditionmay be a virally induced or non-virally induced cutaneous growth orproliferation. The skin condition may be a benign neoplasm,premalignancy or malignancy. The skin condition may be an inflammatorycondition. The skin condition may be a hyperproliferative condition. Theskin condition may be aging including intrinsic (e.g., chronological)and extrinsic changes (e.g., photoaging, ultraviolet light inducedchanges), pigmentary changes, fine lines and rhytides. In someembodiments, the skin condition may be selected from Human PapillomaVirus induced lesions e.g., warts, common warts, palmoplantar warts,flat warts, recurrent warts, recalcitrant warts, treatment naïve warts,epidermodysplasia verruciformis related warts, anogenital warts,condyloma accuminatum, cervical dysplasias or neoplasias, e.g., cervicalintraepithelial neoplasia (CIN); Herpesvirus related lesions includingthose induced by HHV-1 (HSV-1), HHV-2 (HSV-2), HHV-3 (varicella-zostervirus) e.g., chicken pox, Herpes zoster, shingles; Poxvirus inducedlesions e.g., molluscum contagiosum, orf, callus, cutaneous horns,corns, acrochordons, fibroepithelial polyps, prurigo nodularis, actinickeratoses, squamous cell carcinoma, squamous cell carcinoma in situ,keratoacanthoma, basal cell carcinoma, cutaneous lymphomas and benignlymphocytic infiltrates & hyperplasias of the skin, clear cellacanthoma, large cell acanthoma, epidermolytic acanthoma, porokeratosis,hyperkeratosis, keratosis pilaris lichenoid keratosis, acanthosis,acanthosis nigricans, confluent and reticulated papillomatosis, nevi,including e.g., dermal nevi, epidermal nevi, compound nevi, ILVEN(inflammatory linear verrucous epidermal nevi), nevus sebaceous, nevuscomedonicus, and the like; acne, e.g., comedonal acne, inflammatoryacne, papular acne, pustular acne, cystic acne; cysts, e.g., epidermoidcysts, milia, trichilemmal cysts, follicular cysts, proliferating cysts,dermoid cysts, pilonidal cysts, apocrine cysts, eccrine cysts, sebaceouscysts, mucous cysts, myxoid cysts, ganglion cysts, synovial cysts,vellus hair cysts, steatocystoma, hidrocystoma; adnexal neoplasms e.g.,trichofolliculoma, fibrofolliculoma, perifollicular fibroma,trichodiscoma, nevus sebaceous, chondroid syringoma, trichoepithelioma,trichoblastoma, desmoplastic trichoepithelioma, pilomatricoma,pilomatrical carcinoma, tricholemmoma, trichelemmal carcinoma, tumor ofthe follicular infundibulum, tricoadenoma, proliferating pilar tumor,sebaceous hyperplasia, sebaceous adenoma, sebaceous epithelioma,sebaceous carcinoma, syringoma, poroma, hidradenoma, apocrinehidradenoma, spiradenoma, cylindroma, eccrine nevus (eccrine hamartoma),papillary adenoma, papillary adenocarcinoma; benign melanocyticproliferations or neoplasms e.g., ephilides, café-au-lait macules,Becker's melanosis, lentigines, solar lentigines, lentigo simplex,mucosal melanocytic lesions, Mongolian spots, Nevus of Ota, blue nevus,common acquired melanocytic nevi (nevocellular nevus, “moles”),congenital nevi, nevus spilus, recurrent nevi; vascular and perivascularneoplasms and reactive hyperplasias e.g., hemangiomas, cherry angiomas,hobnail hemangiomas (targeted hemosiderotic hemangiomas), tuftedangiomas, hemangioendotheliomas, angiolymphoid hyperplasia witheosinophilia (ALHE), Glomus tumors (glomangiomas), hemangiopericytomas;cutaneous neural and neuroendocrine neoplasms e.g., neuromas,Schwannomas, neurofibromas, nerve sheath tumor, nerve sheath myxoma,neurothekeoma, granular cell tumor; fibrotic and fibrohistiocyticproliferations e.g., acrochordons, fibroepithelial polyps, fibromas,fibrous papules, angiofibromas, pearly penile papules, periungualfibromas, dermatofibromas, fibrokeratomas, sclerotic or pleomorphicfibromas, connective tissue nevi; cutaneous scars, hyperplasias,keloids, rosacea, cutaneous fungal, dermatophyte & mold infections,onychomycosis, hyperpigmentation, rhytides, psoriasis, malignantmelanoma, seborrheic keratosis, seborrheic keratosis variants includinge.g., dermatosis papulosis nigra, inverted follicular keratosis/keratomawarty dyskeratosis/warty dyskeratoma, acrokeratosis verruciformis,stucco keratosis; or a combination thereof.

Some embodiments describe a method of treating warts comprisingadministering a composition having up to about 50% hydrogen peroxide andan alcohol to a subject in need thereof.

Some embodiments describe a method of treating seborrheic keratosiscomprising administering a composition having up to about 50% hydrogenperoxide and an alcohol to a subject in need thereof. In someembodiments, the alcohol is in an amount capable of decreasing thesurface tension of the composition. In some embodiments, the alcohol isin an amount capable of increasing the wettability of the surface of theskin or skin lesion. In some embodiments, the alcohol is in an amountcapable of increasing the permeability of the composition into thesubject's skin and/or the skin lesion. In some embodiments, the alcoholis in an amount capable of enhancing the clinical efficacy of thecomposition. In some embodiments, the alcohol is in an amount capable ofenhancing the clinical efficacy of the composition while maintainingstability sufficient for a commercially viable composition.

Some embodiments herein are directed to a topical solution formulationcomprising up to about 50% hydrogen peroxide and an alcohol. In someembodiments, the solution is comprised of two or more parts to be mixedat or immediately before the time of application.

Some embodiments herein are directed to a gel composition comprising upto about 50% hydrogen peroxide, an alcohol, and a gelling agent. In someembodiments, the gel composition is comprised of two or more parts thatmay be mixed at or immediately before the time of application.

Some embodiments herein describe a composition consisting essentially ofup to about 50% hydrogen peroxide and an alcohol. Some embodimentsherein describe a composition consisting of up to about 50% hydrogenperoxide and an alcohol. In some embodiments, the alcohol is a primaryalcohol, a secondary alcohol, a tertiary alcohol, or a combinationthereof. In some embodiments, the alcohol is not 1-propanol, ethanol,butanol, pentanol, hexanol, octanol, nonanol, decanol, 2-butanol,2-pentanol, or benzyl alcohol. In some embodiments, the alcohol is2-propanol.

Some embodiments herein are directed toward devices for administeringthe compositions of embodiments herein. In some embodiments, the devicesmay include an applicator configured to safely and effectively deliverthe compositions of embodiments herein to the targeted skin of apatient. Some embodiments herein include an applicator configured tostore and dispense a topical composition comprising an agent selectedfrom a caustic agent, an unstable agent or a combination thereof, theapplicator comprising a frangible ampoule having the agent disposedtherein, an applicator body having the frangible ampoule arrangedtherein; an applicator hub in fluid communication with the applicatorbody; a tip arranged at a proximal end of the applicator hub; and afilter arranged between the frangible ampoule and the tip. In someembodiments, the topical composition comprises from about 25% to about50% hydrogen peroxide and up to 5% 2-propanol. In some embodiments, theagent comprises from about 25% hydrogen peroxide to about 50% hydrogenperoxide. In some embodiments, the frangible ampoule further includes upto 5% 2-propanol. In some embodiments, the applicator body furthercomprises an additional ingredient of the topical composition disposedtherein, whereby the agent is released from the frangible ampouleresponsive to the frangible ampoule being ruptured and is mixed with theadditional ingredient in the applicator body prior to administration ofthe topical composition. In some embodiments, the topical composition isreleased from the frangible ampoule responsive to the frangible ampoulebeing ruptured and flows through the applicator body, the filter, andout of the applicator through the tip. In some embodiments, theapplicator further includes a pressure area arranged on an outer surfaceof the applicator body to indicate a portion of the applicator body toapply pressure to rupture the frangible ampoule.

Some embodiments are directed to an applicator configured to store anddispense a topical composition comprising from about 25% to about 50%hydrogen peroxide and up to 5% 2-propanol, the applicator comprising afrangible ampoule having the topical composition disposed therein, anapplicator body having the frangible ampoule arranged therein, anapplicator hub in fluid communication with the applicator body, a tiparranged at a proximal end of the applicator body; and a filter arrangedbetween the frangible ampoule and the tip. In some embodiments, thefrangible ampoule is formed from at least one of glass, plastic,borosilicate glass, Type 1 borosilicate glass, and tinted glass. In someembodiments, the applicator body is formed from polypropylene,high-density polyethylene, low-density polyethylene, polyvinyl chloride,polyethylene, or a combination thereof. In some embodiments, the filteris configured to prevent shards of a ruptured frangible ampoule frompassing through and to allow the topical composition to flow through. Insome embodiments, the filter is formed from at least one ofpolypropylene, high-density polyethylene, low-density polyethylene,polyethylene, polystyrene, a ceramic material, a foam material, sand,diatomaceous earth, and paper fibers.

Some embodiments are directed to a method of treating a skin condition,the method comprising administering a topical composition comprising upto 50% hydrogen peroxide and up to 5% 2-propanol using an applicatorcomprising a frangible ampoule having the topical composition disposedtherein, an applicator body having the frangible ampoule arrangedtherein, an applicator hub in fluid communication with the applicatorbody, a tip arranged at a proximal end of the applicator hub, and afilter arranged between the frangible ampoule and the tip. In someembodiments, administering the topical composition comprises applying asqueezing force to the exterior surface of the applicator body todispense the composition. In some embodiments, administering the topicalcomposition comprises contacting the tip with a targeted lesion of theskin condition whereby the topical composition dispenses through the tiponto the targeted lesion. In some embodiments, administering the topicalcomposition further comprises applying pressure to a pressure areaarranged on an outer surface of the applicator body causing thefrangible ampoule to rupture. In some embodiments, administering thetopical composition comprises causing the frangible ampoule to ruptureand release the topical composition through the tip; and contacting thetip to a targeted lesion of the skin condition.

In some embodiments, the applicator may include a frangible ampouleconfigured to store the compositions of embodiments herein arrangedwithin an applicator body. In some embodiments, the ampoule may beformed from glass or other similar frangible materials, such asborosilicate glass. In some embodiments, the applicator body may beformed from various flexible materials, including, without limitationhigh-density polyethylene (HDPE), low-density polyethylene (LDPE) orvarious combinations or blends thereof. In some embodiments, thecompositions of embodiments herein may be released from the ampoule byapplying manual pressure (for instance, “squeezing”) on the applicatorbody in a direction toward the ampoule sufficient to cause the ampouleto break apart. In some embodiments, the compositions of embodimentsherein released from the ampoule may flow through a filter configured tofilter glass shards from the broken ampoule while allowing thecompositions of embodiments herein to flow therethrough. In someembodiments, at least one portion of the applicator may include ahydrophobic material, such as the filter and/or the tip. In someembodiments the hydrophobic material is composed of polyester orco-polyester polymers, acrylic, modified acrylic (e.g., modacrylic),polypropylene, polyethylene or combinations or mixtures thereof.Non-limiting examples of hydrophobic materials may also includematerials including, coated with, and/or modified by silanes,alkylsilanes, fluoroalkylsilanes, silicone, combinations thereof, andderivatives thereof. In some embodiments, the hydrophobic portions ofthe applicator may operate to impede, reduce, restrict, prevent, and/orsubstantially prevent the compositions of embodiments herein that havebeen released from the ampoule from flowing through portions of theapplicator and/or out of the tip of the applicator. In some embodiments,the compositions of embodiments herein may flow through the filter andout of the applicator via an applicator tip for application on the skinof a patient. In some embodiments, the tip may include a flocked portionformed from filaments of various chemically compatible and non-reactivematerials, such as nylon.

DESCRIPTION OF THE FIGURES

FIG. 1 illustrates the mean cumulative amount of hydrogen peroxidereleased per unit area across silicone membrane (μg/cm²) followingapplication of all 40% w/w hydrogen peroxide formulations. Each timepoint represents the mean±SD (n=5-6).

FIG. 2 illustrates the mean cumulative amount of hydrogen peroxidereleased per unit area across silicone membrane (μg/cm²) followingapplication of 40% w/w hydrogen peroxide formulations containing1-propanol. Each time point represents the mean±SD (n=5-6).

FIG. 3 illustrates the mean cumulative amount of hydrogen peroxidereleased per unit area across silicone membrane (μg/cm²) followingapplication of 40% w/w hydrogen peroxide formulations containing2-propanol. Each time point represents the mean±SD (n=5-6).

FIG. 4 illustrates the steady state release of hydrogen peroxide,calculated between 0.5 and 4 h (μg/cm²/h) following application ofhydrogen peroxide formulations at varying levels of propanol. Each datapoint represents the mean±SD, n=5-6.

FIG. 5 illustrates the difference in the steady state release ofhydrogen peroxide (Flux [1-propanol]−Flux [2-propanol]) for 5, 10, 15and 20% w/w (1-propanol and 2-propanol).

FIG. 6 illustrates the mean surface tension (mN/m) of the differenthydrogen peroxide formulations assessed containing either 1- or2-propanol.

FIG. 7 illustrates the grades and descriptors for the Wart ImprovementAssessment score and the Wart Severity Assessment score.

FIG. 8 illustrates the mean Wart Improvement Assessment score by visit.

FIG. 9 illustrates the mean change in baseline in the Wart SeverityAssessment score by visit.

FIG. 10 illustrates the redox potential (mV) of all 40% w/w hydrogenperoxide formulations containing 1- and 2-propanol, with and withoutskin at t=0, 1, 6 and 24 h. Each time point represents the mean±range,n=3.

FIG. 11 illustrates the redox potential (mV) of 40% w/w hydrogenperoxide formulations containing 5% w/w 1- or 2-propanol, in with andwithout skin at t=0, 1, 6 and 24 h. Each time point represents themean±range, n=3.

FIG. 12 depicts an illustrative applicator according to a firstembodiment.

FIGS. 13A-13C depicts an illustrative applicator according to a secondembodiment.

FIGS. 14A and 14B depict multiple views of an illustrative applicatorbody according to some embodiments.

FIG. 15 depicts an illustrative end cap of an applicator according tosome embodiments.

FIG. 16 depicts an illustrative holed flocked tip (or “applicator hub”)according to some embodiments.

FIGS. 17A and 17B depict an illustrative protective cap according to afirst embodiment.

FIGS. 18A and 18B depict an illustrative protective cap according to asecond embodiment.

DETAILED DESCRIPTION

Before the present compositions and methods are described, it is to beunderstood that this invention is not limited to the particularprocesses, compositions, or methodologies described, as these may vary.It is also to be understood that the terminology used in the descriptionis for the purpose of describing the particular versions or embodimentsonly, and is not intended to limit the scope of the present inventionwhich will be limited only by the appended claims. Unless definedotherwise, all technical and scientific terms used herein have the samemeanings as commonly understood by one of ordinary skill in the art.Although any methods and materials similar or equivalent to thosedescribed herein can be used in the practice or testing of embodimentsof the present invention, the preferred methods, devices, and materialsare now described. All publications mentioned herein are incorporated byreference in their entirety. Nothing herein is to be construed as anadmission that the invention is not entitled to antedate such disclosureby virtue of prior invention.

It must also be noted that as used herein and in the appended claims,the singular forms “a”, “an”, and “the” include plural reference unlessthe context clearly dictates otherwise. Thus, for example, reference toa “skin lesion” is a reference to one or more skin lesions andequivalents thereof known to those skilled in the art, and so forth.

As used herein, the term “about” means plus or minus 10% of thenumerical value of the number with which it is being used. Therefore,about 50% means in the range of 45%-55%.

“Administering”, when used in conjunction with a therapeutic, means toadminister a therapeutic directly into or onto a target tissue or toadminister a therapeutic to a subject, whereby the therapeuticpositively impacts the tissue to which it is targeted. Thus, as usedherein, the term “administering”, when used in conjunction with atherapeutic, can include, but is not limited to, providing a therapeuticto a subject systemically by, for example, intravenous injection,whereby the therapeutic reaches the target tissue. Administering acomposition or therapeutic may be accomplished by, for example,injection, oral administration, topical administration, or by thesemethods in combination with other known techniques. Such combinationtechniques may include heating, radiation, ultrasound and the use ofdelivery agents. Preferably, administering is a self-administration,wherein the therapeutic or composition is administered by the subjectthemselves. Alternatively, administering may be administration to thesubject by a health care provider.

“Providing”, when used in conjunction with a therapeutic, means toadminister a therapeutic directly into or onto a target tissue, or toadminister a therapeutic to a subject whereby the therapeutic positivelyimpacts the tissue to which it is targeted.

The term “animal” as used herein includes, but is not limited to, humansand non-human vertebrates such as wild, domestic and farm animals.

The term “patient” or “subject” as used herein is an animal,particularly a human, suffering from an unwanted disease or conditionthat may be treated by the therapeutic and/or compositions describedherein.

The term “improves” is used to convey that the embodiments providedherein change either the characteristics and/or the physical attributesof the tissue to which the therapeutic composition is being provided,applied or administered. The term “improves” may also be used inconjunction with a diseased state such that when a diseased state is“improved” the symptoms or physical characteristics associated with thediseased state are diminished, reduced or eliminated.

The term “inhibiting” generally refers to prevention of the onset of thesymptoms, alleviating the symptoms, or eliminating the disease,condition or disorder.

“Optional” or “optionally” means that the subsequently described eventor circumstance may or may not occur, and that the description includesinstances where the event occurs and instances where it does not.

As used herein, “room temperature” means an indoor temperature of fromabout 20° C. to about 25° C. (68 to 77° F.).

Throughout the specification of the application, various terms are usedsuch as “primary,” “secondary,” “first,” “second,” and the like. Theseterms are words of convenience in order to distinguish between differentelements, and such terms are not intended to be limiting as to how thedifferent elements may be utilized.

By “pharmaceutically acceptable,” “physiologically tolerable,” andgrammatical variations thereof, as they refer to compositions, carriers,diluents, and reagents or other ingredients of the formulation, can beused interchangeably and represent that the materials are capable ofbeing administered without the production of undesirable physiologicaleffects such as rash, burning, irritation or other deleterious effectsto such a degree as to be intolerable to the recipient thereof.

As used herein, the term “cosmetically acceptable” and grammaticalvariations thereof, as they refer to compositions, carriers, diluents,and reagents or other ingredients of the formulation, represent that thematerials used and final composition are not irritating or otherwiseharmful to the patient in general and to the skin, in particular, andpreferably are pleasant and well tolerated with respect to generalappearance, pH, color, smell and texture (feel), that they are not, forexample, unacceptably sticky (tacky), oily or drying, and that they dospread easily, absorb into the skin at an acceptable rate of absorption,and are generally moisturizing.

As used herein, the term “therapeutic” means an agent utilized to treat,combat, ameliorate, prevent or improve an unwanted condition or diseaseof a subject. In part, embodiments described herein may be directed tothe treatment of various skin diseases, conditions or disorders orsymptoms thereof, including, but not limited to, benign proliferations,neoplasms, premalignancies or malignancies of the skin. The skincondition may be a virally induced or non-virally induced cutaneousgrowth or proliferation. The skin condition may be an inflammatorycondition. The skin condition may be a hyperproliferative condition. Theskin condition may be ageing including intrinsic and extrinsic changes(e.g., photoaging (ultraviolet light induced changes)), pigmentarychanges, fine lines and rhytides. In some embodiments, the skincondition may be selected from Human Papilloma Virus induced lesionse.g., warts, common warts, palmoplantar warts, flat warts, recurrentwarts, recalcitrant warts, treatment naïve warts, epidermodysplasiaverruciformis related warts, anogenital warts, condyloma accuminatum,cervical dysplasias or neoplasias, e.g., cervical intraepithelialneoplasia (CIN); Herpesvirus related lesions including those induced byHHV-1 (HSV-1), HHV-2 (HSV-2), HHV-3 (varicella-zoster virus) e.g.,chicken pox, Herpes zoster, shingles; Poxvirus induced lesions e.g.,molluscum contagiosum, orf; callus, cutaneous horns, corns,acrochordons, fibroepithelial polyps, prurigo nodularis, actinickeratoses, squamous cell carcinoma, squamous cell carcinoma in situ,keratoacanthoma, basal cell carcinoma, cutaneous lymphomas and benignlymphocytic infiltrates & hyperplasias of the skin, clear cellacanthoma, large cell acanthoma, epidermolytic acanthoma, porokeratosis,hyperkeratosis, keratosis pilaris, lichenoid keratosis, acanthosis,acanthosis nigricans, confluent and reticulated papillomatosis, nevi,including e.g., dermal nevi, epidermal nevi, compound nevi, ILVEN(inflammatory linear verrucous epidermal nevi), nevus sebaceous, nevuscomedonicus, and the like; acne, e.g., comedonal acne, inflammatoryacne, papular acne, pustular acne, cystic acne; cysts, e.g., epidermoidcysts, milia, trichilemmal cysts, follicular cysts, proliferating cysts,dermoid cysts, pilonidal cysts, apocrine cysts, eccrine cysts, sebaceouscysts, mucous cysts, myxoid cysts, ganglion cysts, synovial cysts,vellus hair cysts, steatocystoma, hidrocystoma; adnexal neoplasms e.g.,trichofolliculoma, fibrofolliculoma, perifollicular fibroma,trichodiscoma, nevus sebaceous, chondroid syringoma, trichoepithelioma,trichoblastoma, desmoplastic trichoepithelioma, pilomatricoma,pilomatrical carcinoma, tricholemmoma, trichelemmal carcinoma, tumor ofthe follicular infundibulum, tricoadenoma, proliferating pilar tumor,sebaceous hyperplasia, sebaceous adenoma, sebaceous epithelioma,sebaceous carcinoma, syringoma, poroma, hidradenoma, apocrinehidradenoma, spiradenoma, cylindroma, eccrine nevus (eccrine hamartoma),papillary adenoma, papillary adenocarcinoma; benign melanocyticproliferations or neoplasms e.g., ephilides, café-au-lait macules,Becker's melanosis, lentigines, solar lentigines, lentigo simplex,mucosal melanocytic lesions, Mongolian spots, Nevus of Ota, blue nevus,common acquired melanocytic nevi (nevocellular nevus, “moles”),congenital nevi, nevus spilus, recurrent nevi; vascular and perivascularneoplasms and reactive hyperplasias e.g., hemangiomas, cherry angiomas,hobnail hemangiomas (targeted hemosiderotic hemangiomas), tuftedangiomas, hemangioendotheliomas, angiolymphoid hyperplasia witheosinophilia (ALHE), Glomus tumors (glomangiomas), hemangiopericytomas;cutaneous neural and neuroendocrine neoplasms e.g., neuromas,Schwannomas, neurofibromas, nerve sheath tumor, nerve sheath myxoma,neurothekeoma, granular cell tumor; fibrotic and fibrohistiocyticproliferations e.g., acrochordons, fibroepithelial polyps, fibromas,fibrous papules, angiofibromas, pearly penile papules, periungualfibromas, dermatofibromas, fibrokeratomas, sclerotic or pleomorphicfibromas, connective tissue nevi; cutaneous scars, hyperplasias,keloids, rosacea, cutaneous fungal, dermatophyte & mold infections,onychomycosis, hyperpigmentation, rhytides, psoriasis, malignantmelanoma, seborrheic keratosis, seborrheic keratosis variants includinge.g., dermatosis papulosis nigra, inverted follicular keratosis/keratomawarty dyskeratosis/warty dyskeratoma, acrokeratosis verruciformis,stucco keratosis; or a combination thereof.

As used herein, the term “stabilized hydrogen peroxide” refers to ahydrogen peroxide comprising a stabilizer or a blend of stabilizersuseful for dilution of the hydrogen peroxide into a concentration thatcan be incorporated into a stable commercial formulation for topicalapplication to skin lesions for the treatment of skin conditionsdescribed herein. In some embodiments, the hydrogen peroxide may beobtained from a commercial source. The amount and type of stabilizer(s)used in the hydrogen peroxide formulation may be proprietary to and/or atrade secret of the commercial source. In some embodiments, thestabilized hydrogen peroxide is a hydrogen peroxide of highconcentration. Though pure hydrogen peroxides of high concentration aretypically stable, stabilizers may be used in hydrogen peroxideformulations, usually when obtained through commercial sources, in orderto stabilize diluted versions of the “high concentration” hydrogenperoxide formulation. Some hydrogen peroxide formulations havestabilizers in concentrations (in total and/or individually) sufficientto provide stabilization of diluted hydrogen peroxide for particularuses or in particular industries. In some embodiments, the stabilizedhydrogen peroxide has been approved by the Food and Drug Administration(FDA) for topical administration to humans. In some embodiments, thestabilized hydrogen peroxide has a drug master file at the FDA and beenapproved by the FDA for topical administration to humans.

As used herein, the term “clinical efficacy” refers to the ability of aningredient or composition to produce a desired effect. For example, insome embodiments, the desired effect may include, without limitation,decreasing the surface tension of the composition, increasing thewettability of the surface of the skin or skin lesion, increasing thepermeability of the composition into the subject's skin, skin lesion, orsurface imperfections, including crevices, invaginations andirregularities of the skin or skin lesion, decreasing the size of thetarget lesion, improving the shape and/or appearance of the targetlesion, improving the target lesion or treated area and/or removing thetarget lesion, or a combination thereof.

The terms “therapeutically effective” or “effective”, as used herein,may be used interchangeably and refer to an amount of a therapeuticcomposition of embodiments described herein. For example, atherapeutically effective amount of a composition is an amount of thecomposition, and particularly the active ingredient, such as hydrogenperoxide, that generally achieves the desired effect.

A “therapeutically effective amount” or “effective amount” of acomposition is an amount necessary or sufficient to achieve the desiredresult. The activity contemplated by the embodiments herein includesmedically therapeutic, cosmetically therapeutic and/or prophylactictreatment, as appropriate. The specific dose of a compound administeredaccording to embodiments of the present invention to obtain therapeuticand/or prophylactic effects will, of course, be determined by theparticular circumstances surrounding the case, including, for example,the compound administered, the route of administration, and thecondition being treated. However, the effective amount administered canbe determined by the practitioner or manufacturer or patient in light ofthe relevant circumstances including the condition to be treated, thechoice of compound to be administered, and the chosen route ofadministration, and therefore, the above dosage ranges are not intendedto limit the scope of the invention in any way. A therapeuticallyeffective amount of the compound of embodiments herein is typically anamount such that when it is administered in a physiologically tolerableexcipient composition, it is sufficient to achieve an effective systemicconcentration or local concentration in or on the tissue to achieve thedesired therapeutic or clinical outcome.

The terms “treat,” “treated,” or “treating” as used herein refers totherapeutic treatment, cosmetic treatment and/or prophylactic orpreventative measures, wherein the object is to prevent or slow down(lessen) an undesired physiological condition, disorder or disease, orto obtain beneficial or desired clinical results. For the purposes ofthis disclosure, beneficial or desired clinical results include, but arenot limited to, alleviation of symptoms; diminishment of the extent ofthe condition, disorder or disease; stabilization (i.e., not worsening)of the state of the condition, disorder or disease; delay in onset orslowing of the progression of the condition, disorder or disease;amelioration of the condition, disorder or disease state; and remission(whether partial or total), whether detectable or undetectable, orenhancement or improvement of the condition, disorder or disease.Treatment includes eliciting a clinically significant response withoutexcessive levels of side effects.

As used herein, the term “consists of” or “consisting of” means that theformulation or method includes only the elements, steps, or ingredientsspecifically recited in the particular claimed embodiment or claim.

As used herein, the term “consisting essentially of” or “consistsessentially of” means that the formulation or method includes only thespecified materials or steps and those that do not materially affect thebasic and novel characteristics of the claimed invention.

Generally speaking, the term “tissue” refers to any aggregation ofsimilarly specialized cells which are united in the performance of aparticular function.

Seborrheic keratosis (SK) is one of the most common skin tumors in man.These benign epithelial skin tumors are most commonly seen in olderindividuals, increasing in prevalence with increasing age, and affectmen and women roughly equally. The growths may be solitary or occur inlarge numbers and typically present as well demarcated, elevated or“stuck-on” appearing papules or plaques that may vary in color e.g.,from flesh-colored, to shades of yellow, gray, brown, or black. Thoughbenign, they are often cosmetically worrisome to patients, mustsometimes be distinguished from other benign or malignant skin tumors,and may become symptomatic. They may be pruritic, irritated, bleed, andmay be painful when traumatized particularly when located in areas proneto friction and trauma such as belt-lines and brassiere-strap lines.

Patients may seek treatment of SK for cosmetic reasons, especially ifthey are large, pigmented, and/or if multiple lesions are present, orsimply because the lesions are commonly associated with advancing age.Removal may be medically indicated, however, for lesions that becomeirritated, pruritic, inflamed, or painful, or for lesions that theclinician feels require histologic confirmation of the diagnosis.

Numerous surgical treatment options for SK exist, and include a plethoraof destructive/ablative modalities such as, e.g., liquid nitrogencryotherapy, electrodesiccation, lasers of various wavelengths (ablativeand non-ablative), radio-frequency ablation, dermabrasion, and surgicalremoval by curettage or surgical excision. There is, however, a notablelack of well-controlled clinical trials comparing the efficacy,complications and complication rates of these treatments. There is greatvariability among practitioners in the methods employed using each ofthese techniques (e.g., variability in contact time and method offreezing the lesions with liquid nitrogen) with great variability of theresults. None of these treatments is, in fact, approved by the Food andDrug Administration (FDA) for the treatment of seborrheic keratosis.While these methods can achieve cure rates, many require specializedtraining and the use of expensive equipment, they are painful and mayrequire anesthesia and/or analgesia, and they are often complicated bysignificant adverse cosmetic outcomes. Both hypopigmentation andhyperpigmentation, which may be transient, but often permanent, arecommon, as is scarring at the treatment site, and the typicalpost-surgical risks of bleeding and infection increase the risk that theresult of the treatment of these lesions may be worse than the diseaseitself.

Numerous topical medical treatments for SK have been attempted, howeverno topical therapy has been found to be consistently effective. Forexample, ammonium lactate has been found to be ineffective. Otherexamples include calcipotriene ointment, tazarotene cream, imiquimodcream, and Vanicream® applied once daily for 16 weeks, all of which havebeen found to be ineffective. A single report of the off-label use oftazarotene 0.1% applied twice daily, reported efficacy in only 7/15(47%) of subjects, and therapy was complicated by “burning, pruritus andredness”. A report of the use of a topical vitamin D₃ ointment used onceor twice daily for an average of 7.3 months (range 3-12 months) resultedin an 80% or more improvement in lesions in only 30% of patients. Thusthere exists in the art a need for a safe and efficacious topicaltreatment for seborrheic keratosis.

Verrucae (Warts) are virally induced lesions caused by subtypes of theCutaneous Human Papilloma Virus (HPV) family. HPV types are a subset ofthe large group of the DNA papillomavirus family that are capable ofinfecting humans and causing cutaneous lesions. HPV's are ubiquitous inthe environment and infection occurs most commonly as a result of directcontact with individuals who harbor the virus either clinically(evidence lesions) or subclinically, indirectly through exposure tocontaminated surfaces, or by autoinoculation of virus from individuallesions to adjacent uninfected skin. Cutaneous manifestations of HPVinfection include common warts (verruca vulgaris), palmar and plantarwarts, mosaic warts, flat warts, butcher's warts, and others. Subtypesof the HPV family are also etiologic of oropharyngeal, anogenital,laryngeal warts, papillomas, dysplasias (e.g., CIN (cervicalintraepithelial neoplasia) carcinoma in situ, carcinomas, and in theskin lesions seen in epidermodysplasia verruciformis. Common warts aretypically hyperkeratotic, exophytic dome-shaped papules or nodules(typically associated with HPV types 1, 2 or 4) and are most commonlylocated on the fingers (including periungual and subungual regions),dorsal surfaces of the hands, sites prone to trauma (e.g., knees,elbows), but may occur at virtually any other anatomical location. Insome embodiments, the skin condition may be a benign neoplasm,premalignancy or malignancy. The skin condition may be an inflammatorycondition. The skin condition may be a hyperproliferative condition. Theskin condition may be ageing including intrinsic and extrinsic changes(e.g., photoaging (ultraviolet light induced changes)), pigmentarychanges, fine lines and rhytides.

Condyloma acuminata, more commonly known as genital warts, are typicallyrelated to HPV types 6 and 11, 16, 18, and numerous other subtypes(e.g., 33, 35, 39, 40, 43, 45, 51-56, 58 and others), and multiplesubtypes may exist in a single lesion. Condyloma acuminata typicallypresent as solitary to multiple fleshy, soft, verrucoid papules that maybe dome-shaped, filiform, fungating, “cauliflower-like”, or formconfluent plaques. They are typically located in the anogenital region(e.g., penis, vulva, vagina, cervix, perineum, and perianal regions),and may appear in the oropharynx, larynx and even tracheal mucosa, andrarely other cutaneous locations (e.g., trunk, extremities). The lesionsare typically benign, but certain HPV subtypes are associated with arisk of malignant potential (e.g., HPV subtypes 16, 18) and may lead tocutaneous carcinomas or carcinomas-in-situ such as bowenoid papulosis orBuschke-Lowenstein tumor, and cervical dysplasias or neoplasia, e.g.,cervical intraepithelial neoplasia (CIN).

In immunocompetent individuals, many common cutaneous lesions associatedwith HPV infection (e.g., warts and condylomata) spontaneously resolvein less than two years. However, warts can be large and/or cosmeticallyunsightly (e.g., face, hands), spread to distant anatomical regions byautoinoculation, painful (e.g., traumatized or on soles of feet), anduntreated warts provide a significant reservoir of HPV infection in thecommunity.

There are currently no specific antiviral therapies available to treatcutaneous HPV infection. Existing therapies are thus directed towardseither the direct physical destruction of the lesions with locallydestructive modalities such as cryotherapy, electrosurgery, curettage,laser therapy, application of acids (e.g., salicylic acid,trichloroacetic acid); locally cytotoxic therapies, such as topicalpodophyllin, cantharidin, or topical or intralesional 5-fluorouracil, orbleomycin; topical immunomodulatory therapy (e.g., topical imiquimod,intralesional candida antigen, topical squaric acid dibutyl ester, oralcimetidine) or surgical lesion removal. Various of these therapies arealso available as over-the-counter (OTC) wart therapies in lowerconcentrations (e.g., topical salicylic acid preparations; home“freezing” kits). While these methods can achieve cure rates in somecases, many require multiple visits to a physician's office, specializedtraining and the use of expensive equipment; they are painful and mayrequire anesthesia and/or analgesia, and they can be complicated byadverse cosmetic outcomes including scarring at the treatment site, andthe typical post-surgical risks of bleeding and infection. No onetherapy is consistently effective in all cases and in fact, there isgreat variability among practitioners in the methods employed using eachof these techniques with great variability of the results. Recurrencesare common and the use of multiple treatment modalities in combinationis often necessary to achieve significant improvement. Thus, thereexists a great unmet need in the art for a safe and efficacious topicaltreatment for the cutaneous lesions associated with HPV infection e.g.,warts and condyloma.

Mollusca are virally induced lesions caused by subtypes of the DNApoxvirus family of molluscum contagiosum viruses (MCV). There are foursubtypes of MCV, (MCV-1 to 4), with MCV-1 being the most prevalent andMCV-2 being most common in adults. Like HPV's, MCV's are ubiquitous inthe environment and infection occurs most commonly as a result of directcontact with individuals who harbor the virus either clinically(evidence lesions) or subclinically, indirectly through exposure tocontaminated surfaces, or by autoinoculation of virus from individuallesions to adjacent uninfected skin. The infection is most common in thepediatric population, sexually active adults, and the immunocompromised.Molluscum contagiosum lesions are typically flesh-colored, dome-shapedumbilicated (“dimpled”) papules that may occur singly or in clusters andare typically located on the trunk groin or extremities, though mayoccur on any area of the skin. Individual lesions may spontaneouslyresolve in several weeks to several months, however, the natural historyof the infection from appearance of the first lesions to resolution ofthe last lesion may last from six months to five years or more.

There are currently no U.S. Food and Drug Administration approvedtreatments for molluscum contagiosum. There are currently no specificantiviral therapies available to treat cutaneous MCV infection. Existingtherapies are thus directed towards either the direct physicaldestruction of the lesions with locally destructive modalities such ascryotherapy, electrosurgery, curettage, laser therapy, unroofing thelesion with e.g., a needle (“needle-pricking”), application of acids orcaustics (e.g., salicylic acid, potassium hydroxide); locally cytotoxictherapies, such as topical podophyllin, cantharidin; topicalimmunomodulatory therapy (e.g., topical imiquimod, intralesional candidaantigen, nitric acid, oral cimetidine) or surgical lesion removal. Whilethese methods can achieve cure rates in some cases, many requiremultiple visits to a physician's office, specialized training and theuse of expensive equipment; they may be painful and may requireanesthesia and/or analgesia, and may be anxiety producing andpsychologically traumatic, particularly in the pediatric age group.These treatments may be complicated by adverse cosmetic outcomesincluding pigmentary changes (both hyperpigmentation andhypopigmentation), scarring at the treatment site, bleeding andinfection. No one therapy is consistently effective in all cases and infact, there is great variability among practitioners in the methodsemployed using each of these techniques with great variability of theresults. The use of multiple treatment modalities including thetreatment of underlying topical conditions such as atopic dermatitis,which tends to predispose to molluscum and the spread of the lesions, incombination is often necessary to achieve significant improvement. Thus,there exists a great unmet need in the art for a safe and efficacious(topical) treatment for the cutaneous lesions associated with MCVinfection.

Hydrogen peroxide (H₂O₂) is a compound that is ubiquitous in theenvironment. It is the simplest peroxide and a potent oxidizing agentcommonly used in innumerable household goods including chlorine-freebleaches, general-purpose cleaning products, and disinfectants, has beenemployed as the oxidizing component in hair dyes, and has been used inoral hygiene products and tooth-whitening systems for many years. Inindustry, it is employed in the treatment of wastewater and, in highconcentrations, it is used in bleaching paper, pulp, and textiles.Clinically, in addition to its use as an oral topical agent noted above,hydrogen peroxide is widely employed at low concentrations (e.g., 3%-6%)as a wound irrigant and topical antiseptic/disinfectant, and has been inuse medicinally since its introduction into clinical practice byRichardson in 1858.

Hydrogen peroxide is an important oxidizing agent in biological systems.The local deleterious effects of reactive oxygen species on the skin aremitigated by the presence of a complex antioxidant defense system thatincludes, enzymes such as catalase, glutathione peroxidase, superoxidedismutase, thioredoxin reductase, lipoamine, lipid peroxidase andothers, as well as non-enzymatic components including ascorbic acid,urates and uric acid, tocopherol, glutathione, ubiquinones, ubiquinoland other water soluble groups. The local application ofsupra-physiologic concentrations of hydrogen peroxide may overwhelm theantioxidant defense systems in the skin, allowing hydrogen peroxide toact not only through its direct oxidation of organic tissues, generationof reactive oxygen species, and local lipid peroxidation, but also bythe generation of local concentrations of oxygen that are toxic to theabnormal lesional (e.g., seborrheic keratosis, wart, condylomaacuminatum, molluscum contagiosum) cells.

It has been unexpectedly observed that both seborrheic keratosis lesionsand common wart (verruca vulgaris) lesions evidenced a clinical responseafter the application of the compositions of embodiments herein. Incertain cases, clearance of the cutaneous lesion was observed after onesingle treatment. In other cases, e.g., with thicker lesions or largerlesions, two or more treatments may be required for a clinical response.As exemplary benefits of this treatment method, the clinical responsewas brought about without the need for analgesia, without inducing pain,and without inducing the significant adverse events and adverse cosmeticoutcomes commonly resulting from other therapies such as, e.g.,pigmentary changes (such as hypopigmentation or hyperpigmentation),scarring at the treatment site, bleeding or infection.

Embodiments herein generally are directed to compositions comprisinghydrogen peroxide and a surface tension modifying agent. In someembodiments, the surface tension modifying agent is an agent stable incompositions comprising concentrations of hydrogen peroxide disclosed inembodiments herein. In some embodiments, the surface tension modifyingagent is in a quantity sufficient to enhance the therapeutic efficacy ofthe composition. In some embodiments, the surface tension modifyingagent is in a quantity sufficient to enhance the therapeutic efficacy ofthe composition while maintaining stability of the composition. In someembodiments, the surface tension modifying agent is in a quantitysufficient to enhance the therapeutic efficacy of the composition whilemaintaining stability of the composition sufficient for use as acommercially viable formulation. In some embodiments, the surfacetension modifying agent is an alcohol. Embodiments herein are directedto compositions comprising hydrogen peroxide and an alcohol. In someembodiments, the hydrogen peroxide may be a standard grade, food grade,chemical synthesis grade, semiconductor grade, high-test hydrogenperoxide grade, antimicrobial grade, drinking water grade,pharmaceutical grade or cosmetic grade hydrogen peroxide. In someembodiments, the alcohol may be selected from a primary alcohol, asecondary alcohol, a tertiary alcohol, or a combination thereof. In someembodiments, the alcohol may be selected from, but is not limited to, alow molecular weight alcohol, such as methanol, ethanol, butanol,1-propanol, pentanol, hexanol, octanol, nonanol, decanol, 2-butanol,2-propanol, 2-pentanol, benzyl alcohol, an isomer thereof, or acombination thereof. In some embodiments, the alcohol is not 1-propanol,ethanol, propanol, butanol, pentanol, hexanol, octanol, nonanol,decanol, 2-butanol, 2-pentanol, or benzyl alcohol. In some embodiments,the alcohol is 2-propanol (also referred to as isopropyl alcohol). Insome embodiments, other volatiles such as, for example, acetates such asethyl and butyl acetate (volatiles used in nail lacquers),cyclomethicone (a volatile silicone which may be included in anemulsifier system) may be used in combination with or in place of analcohol. Embodiments herein also include a composition consistingessentially of hydrogen peroxide and an alcohol. Some embodiments aredirected to a composition consisting of hydrogen peroxide and analcohol. Some embodiments are directed to a composition comprisinghydrogen peroxide and 2-propanol. Some embodiments are directed to acomposition consisting essentially of hydrogen peroxide and 2-propanol.Some embodiments are directed to a composition consisting of hydrogenperoxide and 2-propanol.

In some embodiments, the hydrogen peroxide is in an amount of up toabout 50% of the composition. In some embodiments, the compositioncomprises hydrogen peroxide in an amount of about 0.5% to about 99.9%,about 10% to about 99.9%, about 20% to about 99.9%, about 30% to about99.9%, about 40% to about 99.9%, about 50% to about 99.9%, about 60% toabout 99.9%, about 70% to about 99.9%, about 80% to about 99.9%, about90% to about 99.9%, about 0.5% to about 70%, about 5% to about 70%,about 10% to about 70%, about 15% to about 70%, about 20% to about 70%,about 25% to about 70%, about 30% to about 70%, about 35% to about 70%,about 40% to about 70%, about 45% to about 70%, about 50% to about 70%,about 55% to about 70%, about 60% to about 70%, about 65% to about 70%,up to about 50%, about 0.5% to about 50%, about 5% to about 50%, about10% to about 50%, about 15% to about 50%, about 20% to about 50%, about23.5% to about 50%, about 25% to about 50%, about 30% to about 50%,about 35% to about 50%, about 40% to about 50%, or about 45% to about50%. In some embodiments, the hydrogen peroxide may be in an amount ofabout 0.5%, 5%, 10%, 15%, 20%, 23.5%, 25%, 30%, 32.5%, 35%, 40%, 45%,50%, 55%, 60%, 65%, 70%, or a range between any two of these values.

In some embodiments, the hydrogen peroxide may be a stabilized hydrogenperoxide. In some embodiments, the hydrogen peroxide may be a standardgrade, food grade, chemical synthesis grade, semiconductor grade,high-test hydrogen peroxide grade, antimicrobial grade, drinking watergrade, pharmaceutical grade or cosmetic grade hydrogen peroxide. In someembodiments, the hydrogen peroxide may be a stabilized pharmaceuticalgrade hydrogen peroxide. In some embodiments, the hydrogen peroxide maybe a stabilized cosmetic grade hydrogen peroxide. In some embodiments,the hydrogen peroxide is FMC/PeroxyChem “Super D” 50% cosmetic gradehydrogen peroxide. In some embodiments, the hydrogen peroxide isFMC/PeroxyChem's “High-Test Hydrogen Peroxide,” which includesstabilized 50%, 70%, and 90% hydrogen peroxide. In some embodiments, thehydrogen peroxide is Arkema Peroxal 50 CG. In some embodiments, thestarting hydrogen peroxide concentration is at a concentrationsufficient to be diluted to a concentration of about 23% hydrogenperoxide or above in the compositions described herein. In someembodiments, the stabilized hydrogen peroxide has stabilizers in aconcentration sufficient to prevent the breakdown/degradation of thehydrogen peroxide when it is diluted to a concentration of about 23%hydrogen peroxide or above in the compositions described herein. In someembodiments, the stabilized hydrogen peroxide has stabilizers in aconcentration sufficient to prevent the breakdown/degradation of thesurface-tension modifying agent (e.g., alcohol such as 2-propanol) whenit is diluted to a concentration of about 23% hydrogen peroxide or abovein the compositions described herein. In some embodiments, thestabilized hydrogen peroxide has stabilizers in a concentrationsufficient to ensure the stability of the composition to be packaged inan appropriate packaging system, container, or applicator, and to besuitable for commercial use as contemplated in embodiments describedherein. For example, in some embodiments, a method of making thecomposition may comprise a step or steps that the stabilized hydrogenperoxide be diluted down to, e.g., 45%, or 40% or 32.5%, or 25%, in thefinal composition. In this scenario, the starting hydrogen peroxideformulation should have a sufficiently high concentration to be able tobe diluted to, e.g., 45%, or 40%, or 32.5%, or 25%, with the addition ofwater such as deionized water and an additional excipient or excipientssuch as a surface-tension modifying agent such as an alcohol (e.g.,2-propanol, or the like), as described in embodiments herein, such thatit is sufficiently stabilized in order to guarantee a shelf-lifesuitable to produce a commercially viable formulation.

Hydrogen peroxide is a compound which is highly susceptible todecomposition by the presence of dissolved impurities, mostly transitionmetal cations and mixtures based on hydrogen peroxide may be unstable,with the hydrogen peroxide concentration diminishing over time due tocatalytic decomposition. Impurities causing hydrogen peroxidedecomposition are typically contained in water used to dilute theaqueous hydrogen peroxide stock formulation to a desired concentrationor in the additional excipients added to the formulation (e.g.,2-propanol). A variety of factors may influence the stability ofhydrogen peroxide in solutions, including, for example, the temperature,the concentration of hydrogen peroxide, the pH value, and the presenceof impurities having a decomposing effect. To limit the influence ofsuch decomposing factors on stability, it has been discovered that, insome embodiments, a stabilized composition having commercial value forthe treatment of the multiple skin conditions described herein, e.g.,seborrheic keratosis, warts, condyloma acuminatum, molluscumcontagiosum, may be achieved by the careful selection of a concentrationof 2-propanol and a stabilized (e.g., cosmetic grade) of highconcentration (e.g., 50%) aqueous hydrogen peroxide solution.Accordingly, in some embodiments, the composition may comprise astabilizer or combination of stabilizers. Hydrogen peroxide productsfrom different sources may differ because of a proprietary blend ofstabilizers unique to each company and to each product line within eachcompany, and may importantly affect the stability and performance of thefinal product. Stabilizer levels for each individual stabilizer may varyfrom above 0 mg/ml to several thousand mg/1 each depending on the gradeof the hydrogen peroxide, the concentration of the peroxide, and thechoice of stabilizers used. In some embodiments, the hydrogen peroxideis supplied by FMC Industrial Chemicals® (now PeroxyChem, LLC.), SigmaCorporation®, Arkema Incorporated®, or the like. In some embodiments,the hydrogen peroxide is supplied by PeroxyChem, LLC. In someembodiments, the hydrogen peroxide is FMC/PeroxyChem “Super D” 50%Cosmetic Grade hydrogen peroxide. Common stabilizers included inhydrogen peroxide formulations may include a stannate (e.g., colloidalstannate, sodium stannate), sodium pyrophosphate, organophosphonates,nitrate, phosphoric acid, colloidal silicate, any other stabilizer knownin the art, or a combination thereof. In some embodiments, eachstabilizer may be in a concentration of above 0 ppm to about 5000 ppm.In some embodiments, each stabilizer may be in a concentration of above0 ppm to about 3000 ppm. In some embodiments, each stabilizer may be ina concentration of about 70 ppm to about 5000 ppm. In some embodiments,each stabilizer may be in a concentration of about 70 ppm to about 3000ppm. In some embodiments, each stabilizer may be in a concentration ofabout 70 ppm to about 2700 ppm. In some embodiments, each stabilizer maybe in a concentration of about 270 ppm to about 5000 ppm. In someembodiments, each stabilizer may be in a concentration of about 300 ppmto about 5000 ppm. In some embodiments, each stabilizer may be in aconcentration of about 270 ppm to about 3000 ppm. In some embodiments,each stabilizer may be in a concentration of about 300 ppm to about 3000ppm. In some embodiments, each stabilizer may be in a concentration ofabout 300 ppm to about 2700 ppm. In some embodiments, each stabilizermay be in a concentration of about 270 ppm to about 2700 ppm.

The hydrogen peroxide in compositions of embodiments herein may bereplaced with or combined with other peroxides. Other peroxides mayinclude, but are not limited to, sodium peroxide, potassium peroxide andpotassium superoxide, lithium peroxide, barium peroxide, calciumperoxide, magnesium peroxide, zinc peroxide, tert-butyl hydroperoxide,peracetic acid, dibenzyl peroxide, benzoyl peroxide, lauroyl peroxide,or a combination thereof.

Water, organic solvents such as alcohols, surfactants, and other agentsmay alter the surface tension of compositions, formulations, and mostparticularly of solutions. However, little is known about the effects oflow concentrations of alcohols or other volatiles on the wettability ofnormal skin when alcohol/water mixtures are applied, and there have beenno reports on the effects of different concentrations of alcohols orother volatiles when incorporated into formulations comprising hydrogenperoxide on the wettability of normal skin or of the wettability ofabnormal or lesional skin—such as skin that has been affected byseborrheic keratosis, warts, condyloma accuminatum, molluscumcontagiosum, or other virally induced or non-virally induced cutaneousgrowths or lesions, including those skin conditions listed herein.Without being bound by theory, it is believed that the inclusion ofalcohol in a stabilized peroxide solution may serve several importantfunctions: The incorporation of a low concentration of the alcohol,e.g., less than 15% 2-propanol, may allow for the incorporation of atherapeutically effective concentration of hydrogen peroxide (e.g., 25%to 45% hydrogen peroxide), where the hydrogen peroxide may be insufficient concentration to achieve the desired therapeutic effect onthe cutaneous lesions, and the alcohol is in an amount sufficient todecrease the surface tension of the formulation and to increase thewettability of the surface of the skin lesion to allow spread of theformulation over the surface and into the surface irregularities of thelesion. However, secondary alcohols (e.g., isopropanol (IPA)) areexpected to be inherently less stable in high concentrations of hydrogenperoxide than primary alcohols (see below), that is, 2-propanol isexpected to be more readily oxidized in high concentrations of hydrogenperoxide than is 1-propanol, and the incorporation of low concentrationsof a secondary alcohol (IPA) in a concentration sufficient to fulfillthe above requirements (decrease surface tension/increase wettability ofthe skin lesion/maintain or enhance therapeutic efficacy) and allow thecreation of a stable, commercially viable formulation was challenging.

It was surprisingly discovered that 2-propanol, in an amount that may besufficient to decrease the surface tension of the formulation, mayincrease the wettability of the surface of the skin lesions, and maymaintain or enhance the therapeutic effect of the formulation on theconditions that are the subject of this application, may be stablyincorporated into a highly concentrated hydrogen peroxide solution. Asnoted above, isopropanol, a secondary alcohol, is expected to be moreeasily oxidized than 1-propanol, the primary alcohol in the presence ofhigh concentrations of hydrogen peroxide. The mechanism of the oxidationof alcohols in high concentrations of hydrogen peroxide is first, thegeneration of hydroxyl radicals from the decomposition of the hydrogenperoxide. This process can be accelerated by the presence of catalyticmetals or other catalysts such as those that might be introduced by theaddition of excipients &/or impurities (mainly transition metalcations). The hydroxyl radical would then abstract a hydrogen atom fromthe carbon adjacent to the oxygen on the alcohol molecule, resulting ina carbon radical. In the case of isopropanol, this is a secondaryradical which is stabilized by the electrons on the oxygen and bothmethyl groups next to the carbon. For 1-propanol, this is a primaryradical with just one alkyl group next to it, which is less stable andmore difficult to form. This intermediate would lose the hydrogen atomof the hydroxyl group to form ketone or aldehyde and the aldehyde,propanal from 1-propanol, can be further oxidized to propionic acid. Inpreparations of hydrogen peroxides that are of high purity and arehighly stabilized or have high concentrations of stabilizers (and withlower concentrations of catalyst/impurities), the decomposition ofperoxide may be slowed and thus the decomposition of the includedalcohol may be slowed. Though without an obvious catalyst, thedecomposition of peroxide is slow. The apparent reaction rate might becomplex equation involving any trace catalyst (e.g., catalytic metal),peroxide and alcohol concentrations, but considering the alcohol alone,a secondary alcohol is more easily oxidized than the primary one. It wassurprisingly discovered, however, that by employing a stabilizedformulation of hydrogen peroxide (e.g., FMC/PeroxyChem “Super D”), theincorporation of low concentrations of the secondary alcohol 2-propanol(IPA) into a stable, commercially viable formulation, was indeedpossible. Additionally and importantly, primary alcohols, such as1-propanol are known to provoke cutaneous erythema (redness) andirritation of the skin and may produce a “flushing reaction” whenapplied to the skin due to the generation of aldehyde intermediates ofprimary alcohol breakdown. Alcohol dehydrogenase (ADH), which is presentin the skin, acts on and breaks down primary alcohols, such as1-propanol, but does not act on secondary alcohols, such as 2-propanol.Thus, only primary alcohols, which can be oxidized to the correspondingaldehydes by alcohol dehydrogenase (ADH) present in the skin, and notsecondary (or tertiary) alcohols, elicit this cutaneous erythemareaction by this important mechanism. By incorporating a secondaryalcohol such as 2-propanol (rather than a primary alcohol such as1-propanol) into the composition, adverse cutaneous erythematousreactions resulting from or exacerbated by ADH catalyzed aldehydeintermediates may be avoided or mitigated.

It was thus surprisingly discovered that the addition of lowerconcentrations of alcohol, such as those described in embodimentsherein, and particularly 2-propanol, to hydrogen peroxide increased thewettability of the skin lesion. Additionally, skin lesions, by nature,may have crevices and/or invaginations or surface irregularities thatmay make penetration of the hydrogen peroxide difficult. Accordingly, insome embodiments, a composition may comprise a hydrogen peroxide and asurface tension modifying agent. In some embodiments, the surfacetension modifying agent may be an alcohol. The alcohol may be in anamount sufficient to decrease the surface tension of the composition toa level that effectively increases the penetration of the compositioninto such crevices and/or invaginations of the skin lesion, increase thesurface area of reaction and increase the therapeutic efficacy and/orclinical response of the skin lesion to the therapeutic composition. Insome embodiments, the composition further comprises anothersurface-tension modifying agent. In some embodiments, the surfacetension modifying agent may be selected from, without limitation, asurfactant, e.g., an anionic or nonionic surfactant, a water-solublesurfactant such as a polysorbate, SLS (sodium lauryl sulfate),polypropylene glycol (PPG) stearate such as Arlamol, PEG (polyethyleneglycol) stearate, steareth, ceteareth, polyoxyl stearate, or the like,or a combination thereof. The surface tension modifying agent may be inan amount sufficient to decrease the surface tension of the compositionto a level that effectively increases the penetration of the compositioninto the crevices, invaginations and/or surface irregularities of theskin lesion, increases the surface area of reaction, and increases thetherapeutic efficacy and/or clinical response of the skin lesion to thetherapeutic composition, or a combination thereof.

In particular, it was surprisingly discovered that 2-propanol is aparticularly effective alcohol for incorporation in the compositionsdescribed herein. In fact, it was unexpectedly discovered that2-propanol is a more suitable and effective alcohol in the compositionsdescribed herein than 1-propanol. 1-propanol does allow for release ofhydrogen peroxide, may reduce the surface tension of the composition toincrease penetration of the composition into the skin, and was expectedto be more stable (i.e. less likely to be oxidized) in formulationscomprising high concentrations of hydrogen peroxide. In fact, whencompared to 2-propanol, 1-propanol does, in some concentrations, provideincreased release or increased rate of release of hydrogen peroxide andmay reduce surface tension more (on a weight to weight basis). However,it was surprisingly discovered that despite its seemingly potentialdesirable effects, 1-propanol is actually a less effective alcohol than2-propanol in compositions of embodiments disclosed herein. Withoutwishing to be bound by theory, it is believed that (i) though there is atrend towards 1-propanol containing compositions to release morehydrogen peroxide where 1-propanol is in higher concentrations,2-propanol containing compositions effectively release hydrogen peroxideand exhibit a more constant rate of release across the desiredconcentrations in the embodiments described herein; (ii) though1-propanol may reduce the surface tension of the hydrogen peroxideformulation more, on a weight for weight basis, than 2-propanol, thesurface tension reduction induced in the compositions of the preferredembodiments by 1-propanol is excessive and suboptimal as it may inducesuch a great reduction that the composition would undesirably spread offthe target lesion or area and onto surrounding non-lesional skin,leading to adverse effects such as irritation and erythema due at leastin part to the generation of undesirable aldehyde intermediates asdiscussed above; and (iii) though theoretically, as discussed, theprimary alcohol, 1-propanol, would be expected to exhibit greaterstability in high concentration hydrogen peroxide formulations than thesecondary alcohol (i.e. 2-propanol), 1-propanol appears to be oxidizedto a greater degree by hydrogen peroxide in the high concentrationhydrogen peroxide formulations of the preferred embodiments than is2-propanol, and is, in fact, less stable. Thus, the incorporation of2-propanol in compositions described herein provides for significantadvantages over the incorporation of 1-propanol, including, but notlimited to, providing for a therapeutically effective formulation whichis more stable—leading to improved clinical efficacy of the composition,lower tendency to spread away from the intended site of application and,therefore, a more favorable safety profile

The amount of alcohol in the composition may also be limited by theperoxide concentration in the formulation. For example, if a highconcentration of peroxide is desired, the concentration of alcohol maynecessarily be lowered in order to maintain the high concentration ofperoxide in the formulation. In some embodiments, the alcohol may be inan amount sufficient to decrease the surface tension of the composition,to increase the penetration of the composition into the crevices and/orinvaginations of the skin lesion, increase the surface area of reactionand increase the therapeutic efficacy and/or clinical response of theskin lesion to the therapeutic composition. In some embodiments, theformulation does not spread undesirably onto the surroundingnon-lesional unaffected skin, which may occur with too large an amountof alcohol or too great a reduction in surface tension. In someembodiments the formulation does not irritate the surrounding,non-lesional, unaffected skin. In some embodiments, the formulation doesnot cause erythema to surrounding non-lesional unaffected skin. Erythemaand irritation of the surrounding, non-lesional, unaffected skin may becaused by generation of irritating, erythema inducing intermediates,such as aldehydes, which may be due to the breakdown of suboptimalalcohols in the composition (e.g., primary alcohols, such as1-propanol).

In some embodiments, the composition comprises a surface tensionmodifying agent. In some embodiments, the surface tension modifyingagent is an alcohol. In some embodiments, the surface tension modifyingagent is in an amount sufficient to decrease the surface tension of thehydrogen peroxide and water formulation. In some embodiments, thecomposition comprises an alcohol in an amount sufficient to decrease thesurface tension of the hydrogen peroxide and water formulation. In someembodiments, the alcohol is a primary alcohol, a secondary alcohol, atertiary alcohol, or a combination thereof. In some embodiments, thesecondary alcohol is 2-propanol. Without alcohol, such as 2-propanol, todecrease the surface tension, the hydrogen peroxide-water formulationmay sit on the surface of the lesion, without penetrating the lesionand/or the surface imperfections, irregularities, crevices of thelesion. In some embodiments, the surface tension modifying agent may bein an amount sufficient to decrease the surface tension of thecomposition to a level that effectively increases the penetration of thecomposition into such crevices and/or invaginations of the skin lesion,increase the surface area of reaction, increase the therapeutic efficacyand/or clinical response of the skin lesion to the therapeuticcomposition while minimizing irritation of the surrounding skin, or anycombination thereof. Furthermore, alcohols that lower the surfacetension of hydrogen peroxide composition excessively may run the risk ofeasily spreading off the application site and across non-lesional skin,causing less activity at the needed site and unwanted irritation andother adverse effects on the surrounding, unaffected skin.

In some embodiments, the alcohol in compositions of embodiments hereinmay be replaced with other volatile agents. Such volatile agents mayinclude, but are not limited to, volatiles such as acetates, e.g., ethylacetate and butyl acetate (volatiles used in nail lacquers),cyclomethicone (a volatile silicone which may be included in anemulsifier system), and various other volatiles in addition to thoseshown and described herein, which will become apparent to those skilledin the art from the foregoing description. Such additional volatileagents may be used in combination with or in place of an alcohol.

In some embodiments, the alcohol may be selected from a primary alcohol,a secondary alcohol, a tertiary alcohol, or a combination thereof. Insome embodiments, the alcohol may include methanol, ethanol, butanol,1-propanol, pentanol, hexanol, octanol, nonanol, decanol, 2-butanol,2-propanol, 2-pentanol, benzyl alcohol, an isomer thereof or acombination thereof. In some embodiments, the alcohol is 2-propanol.Though embodiments herein may refer to 2-propanol in particular, oneskilled in the art would understand that other alcohols and/orvolatiles, such as, but not limited to, those described above may beused in place of 2-propanol in such embodiments.

2-propanol (also referred to as isopropyl alcohol) is a chemicalcompound with the molecular formula C₃H₈O or C₃H₇OH. It is a colorless,flammable chemical compound with a strong odor. It is the simplestexample of a secondary alcohol, where the alcohol carbon atom isattached to two other carbon atoms sometimes shown as (CH₃)₂CHOH. It isa structural isomer of propanol. 2-propanol is miscible in water,alcohol, ether and chloroform. It will dissolve ethyl cellulose,polyvinyl butyral, many oils, alkaloids, gums and natural resins. It isinsoluble in salt solutions. Unlike ethanol or methanol, 2-propanol maybe separated from aqueous solutions by adding a salt such as sodiumchloride, sodium sulfate, or any of several other inorganic salts, sincethe alcohol is much less soluble in saline solutions than in salt-freewater. 2-propanol has many medical and pharmaceutical uses and istypically used topically in concentrations of about 60% to about 70% inwater as a topical disinfectant and in concentrations of about 60% toabout 75% v/v solution in gels as a hand sanitizer. 2-propanol is alsoused as a water-drying aid for the treatment/prevention of otitisexterna (swimmer's ear) in a concentration of up to 95%.

In some embodiments, the alcohol is in an amount of up to about 0.1%, upto about 0.25%, up to about 0.5%, up to about 1%, up to about 2%, up toabout 2.5%, up to about 3%, up to about 4%, up to about 5%, up to about8%, up to about 10%, up to about 14%, up to about 15%, up to about 20%,or up to about 25% of the composition. The use of low concentrations ofalcohol, e.g., 2-propanol, as described in embodiments herein, allowsfor the use of stabilized hydrogen peroxides of therapeutically highconcentrations (such as greater than 23%) of hydrogen peroxide, suchthat the stabilizers in the hydrogen peroxide are able to maintain thechemical stability of the formulation without being affected by thealcohol (and its impurities). In some embodiments, the alcohol maycomprise up to about 25% of the composition. In some embodiments, thealcohol may be in an amount of about 0.05% to about 25%, about 0.5% toabout 25%, about 1% to about 25%, about 2.5% to about 25%, about 5% toabout 25%, about 10% to about 25%, about 15% to about 25%, or about 20%to about 25%, about 0.05% to about 15%, about 0.5% to about 25%, up toabout 5%, about 0.01% to about 5%, about 0.1% to about 5%, about 0.5% toabout 5%, about 1% to about 5%, about 1.5% to about 5%, about 2% toabout 5%, about 2.5% to about 5%, about 3% to about 5%, about 3.5%, toabout 5%, about 4% to about 5%, about 4.5% to about 5%, or the like. Insome embodiments, the alcohol may be in an amount of about 0.01%, 0.1%,0.25%, 0.5%, 0.75%, 1%, 2%, 2.5%, 3%, 4% 5%, 10%, 15%, 20%, 25%, or arange between any two of these values. In some embodiments, thecomposition comprises about 40% hydrogen peroxide and about 5% alcohol.In some embodiments, the composition comprises about 45% hydrogenperoxide and about 5% alcohol. In some embodiments, the compositioncomprises about 35% hydrogen peroxide and about 5% alcohol. In someembodiments, the composition comprises about 32.5% hydrogen peroxide andabout 5% alcohol. In some embodiments, the composition comprises about25% hydrogen peroxide and about 5% alcohol. In some embodiments, thecomposition comprises about 40% hydrogen peroxide and about 2.5%alcohol. In some embodiments, the composition comprises about 45%hydrogen peroxide and about 2.5% alcohol. In some embodiments, thecomposition comprises about 35% hydrogen peroxide and about 2.5%alcohol. In some embodiments, the composition comprises about 32.5%hydrogen peroxide and about 2.5% alcohol. In some embodiments, thecomposition comprises about 25% hydrogen peroxide and about 2.5%alcohol. In some embodiments, the composition comprises about 40%hydrogen peroxide and about 2% alcohol. In some embodiments, thecomposition comprises about 45% hydrogen peroxide and about 2% alcohol.In some embodiments, the composition comprises about 35% hydrogenperoxide and about 2% alcohol. In some embodiments, the compositioncomprises about 32.5% hydrogen peroxide and about 2% alcohol. In someembodiments, the composition comprises about 25% hydrogen peroxide andabout 2% alcohol. In some embodiments, the alcohol is 2-propanol.

In some embodiments, the composition consists essentially of up to about50% hydrogen peroxide and an alcohol. In some embodiments, thecomposition consists essentially of about 40% hydrogen peroxide andabout 5% alcohol. In some embodiments, the composition consistsessentially of about 45% hydrogen peroxide and about 5% alcohol. In someembodiments, the composition consists essentially of about 35% hydrogenperoxide and about 5% alcohol. In some embodiments, the compositionconsists essentially of about 32.5% hydrogen peroxide and about 5%alcohol. In some embodiments, the composition consists essentially ofabout 25% hydrogen peroxide and about 5% alcohol. In some embodiments,the composition consists of up to about 50% hydrogen peroxide and analcohol. In some embodiments, the composition consists of about 40%hydrogen peroxide and about 5% alcohol. In some embodiments, thecomposition consists of about 45% hydrogen peroxide and about 5%alcohol. In some embodiments, the composition consists of about 35%hydrogen peroxide and about 5% alcohol. In some embodiments, thecomposition consists of about 32.5% hydrogen peroxide and about 5%alcohol. In some embodiments, the composition consists of about 25%hydrogen peroxide and about 5% alcohol. In some embodiments, the alcoholis 2-propanol.

In some embodiments, the alcohol decreases the surface tension of thecomposition. In some embodiments, the alcohol increases the penetrationof the hydrogen peroxide into the skin imperfections of the subject,such as the irregularities, crevices and imperfections of the skin orskin lesion. In some embodiments, the alcohol defats the subject's skinor skin lesion of the subject, thereby allowing better penetration ofthe hydrogen peroxide into the subject's skin or skin lesion. In someembodiments, the alcohol increases the wettability of the surface of theskin, including the wettability of the skin growth or lesion.

In some embodiments, the alcohol increases the effective concentrationof the hydrogen peroxide when administered. Hydrogen peroxide isbactericidal, virucidal, sporocidal, and fungicidal, and may be asterilant at varying concentrations and contact times. In someembodiments, the hydrogen peroxide is in a concentration sufficient tobe virucidal. In some embodiments the hydrogen peroxide has sufficientcontact time with the skin or skin lesion for it to exhibit itsbactericidal, virucidal, sporocidal, fungicidal or sterilant effects. Insome embodiments, the hydrogen peroxide has sufficient contact time withthe skin or skin lesion sufficient for it to exhibit virucidal effects.Without being bound by theory, the alcohol may increase the effectiveconcentration of the hydrogen peroxide when it evaporates after beingadministered, and may increase the oxidative and/or germicidal activityof the formulation. Additionally, the increased penetration of theformulation may increase the surface area or contact time of thesolution with the skin or skin lesion and lead to enhanced effect as agermicide or sterilant.

In some embodiments, the composition may be administered topically. Insome embodiments, the composition may be a solution. In someembodiments, the composition may be in a gel formulation. In someembodiments, the solution or gel formulation may be in two or more partsto be admixed at or immediately before the time of administration. Insome embodiments, the composition may be in a cream, lotion, ointment,foam, transdermal patch, powder, solid, tape, paste or tincture. In someembodiments, the methods of treating described in embodiments hereinrequire only one single application of the composition of embodimentsherein. In some embodiments, the methods of treating described inembodiments herein require two or more applications of the compositionof embodiments herein. In some embodiments, the methods of treatingdescribed in embodiments herein require multiple applications of thecomposition of embodiments herein.

In some embodiments, the composition may further include apharmaceutically acceptable excipient. In some embodiments, thecomposition may further include an emollient, an emulsifier, a gellingagent, an additive, or a combination thereof. In some embodiments, theadditive may be selected from preservatives, emulsion stabilizers, pHadjusters, chelating agents, viscosity modifiers, anti-oxidants,surfactants, detergents, emollients, opacifying agents, skinconditioners, buffers, or a combination thereof.

Some embodiments herein are directed to a gel formulation comprisinghydrogen peroxide, and a gelling agent. In some embodiments, the gelformulation may further comprise an alcohol. In some embodiments, thegel formulation may further comprise a pharmaceutically acceptableexcipient. In some embodiments, the gelling agent may be selected fromCarbopol ETD 2020, Carbopol 980 NF, Carbopol 974P, Carbopol Ultrez 10,or the like. In some embodiments, the gelling agent may be highmolecular weight, cross linked copolymers of acrylic acid and ahydrophobic comonomer or a copolymer (e.g., Pemulen TR-1); PolycarbophilAA-1; PVP (polyvinyl pyrrolidone); Eudragit; Poloxamer; Sepineo;Bentonite; Aerosil (silicates); Hyaluronic Acids; cross-linkedHyaluronic Acids; a combination thereof, or a compositional or chemicalequivalent thereof possessive of the qualities required for thecomposition of embodiments described herein. In some embodiments, thegel composition is kept in two-parts and mixed at or immediately beforethe time of application. For example, the hydrogen peroxide and2-propanol (first part) could be kept separate from the gelling agent(second part) until the time of administration or immediately before. Asanother example, the hydrogen peroxide, 2-propanol and gelling agentcould each be separated into three parts and mixed at or immediatelybefore the time of application. Additional parts may be possible foradditional excipients or such excipients may be incorporated intoexisting parts. At or immediately before the time of administration, themulti-part gel formulation may be mixed and applied topically to theskin as a single gel formulation.

Some embodiments are directed to a gel formulation that may be deliveredin an applicator that mixes two or more components of the gelformulation at or immediately before the time of application. In someembodiments, the gel formulation compartment applicator comprises atleast one frangible compartment (e.g., gelling agent in the maincompartment of the applicator, with the peroxide in a glass ampulewithin or alongside that compartment). Some exemplary applicators mayinclude syringe-like applicators or “double-barrel” applicators that canfreshly mix (e.g., “vortex mix”) two or more components that need to beheld in separate compartments for stability reasons, but which can bemixed at or immediately before the time of application.

In some embodiments, the composition further includes a buffer. In someembodiments, the buffer may be selected from triethanolamine, low pHbuffers such as sodium acetate, citrate, phosphate, glycine, hydrogenchloride, citrate and phosphate, glycine and hydrogen chloride, thelike, or a combination thereof. In some embodiments, the buffer may bepresent in an amount of about 0.001% to about 15%. In some embodiments,the buffer is present in an amount of about 0.001%, 0.01%, 0.05%, 0.1%,0.5%, 1%, 5%, 10%, 15%, or a range between any two of these values. Insome embodiments the buffer is present in any amount necessary tooptimally adjust the pH of the composition.

In some embodiments, the composition has a surface tension of about 15mN·m−1 to about 80 mN·m−1 at room temperature. In some embodiments, thecomposition has a surface tension of about 20 mN·m−1 to about 80 mN·m−1,about 30 mN·m−1 to about 80 mN·m−1, about 40 mN·m−1 to about 80 mN·m−1,about 50 mN·m−1 to about 80 mN·m−1, about 35 mN·m−1 to about 80 mN·m−1,about 35 mN·m−1 to about 70 mN·m−1, about 35 mN·m−1 to about 60 mN·m−1,about 35 mN·m−1 to about 50 mN·m−1 at 37° C., about 40 mN·m−1 to about80 mN·m−1, about 40 mN·m−1 to about 70 mN·m−1, about 40 mN·m−1 to about60 mN·m−1, about 40 mN·m−1 to about 50 mN·m−1, about 45 mN·m−1 to about80 mN·m−1, about 45 mN·m−1 to about 70 mN·m−1, about 45 mN·m−1 to about60 mN·m−1, or about 45 mN·m−1 to about 50 mN·m−1 at room temperature. Insome embodiments, the composition has a surface tension of about 15mN·m−1, about 20 mN·m−1, about 30 mN·m−1, about 36 mN·m−1, about 41mN·m−1, about 48 mN·m−1, about 54 mN·m−1, about 75 mN·m−1, about 40mN·m−1, about 50 mN·m−1, about 60 mN·m−1, about 70 mN·m−1, about 80mN·m−1, or a range between any two of these values at room temperature.In some embodiments, the composition has a surface tension of about 42mN·m−1 to about 55 mN·m−1 at room temperature. In some embodiments, thecomposition has a surface tension of about 42 mN·m−1 to about 50 mN·m−1at room temperature.

In some embodiments, the composition has a surface tension of about 15mN·m−1 to about 80 mN·m−1 at 37° C. In some embodiments, the compositionhas a surface tension of about 20 mN·m−1 to about 80 mN·m−1, about 30mN·m−1 to about 80 mN·m−1, about 40 mN·m−1 to about 80 mN·m−1, about 50mN·m−1 to about 80 mN·m−1, about 35 mN·m−1 to about 80 mN·m−1, about 35mN·m−1 to about 70 mN·m−1, about 35 mN·m−1 to about 60 mN·m−1, about 35mN·m−1 to about 50 mN·m−1 at 37° C., about 40 mN·m−1 to about 80 mN·m−1,about 40 mN·m−1 to about 70 mN·m−1, about 40 mN·m−1 to about 60 mN·m−1,about 40 mN·m−1 to about 50 mN·m−1, about 45 mN·m−1 to about 80 mN·m−1,about 45 mN·m−1 to about 70 mN·m−1, about 45 mN·m−1 to about 60 mN·m−1,or about 45 mN·m−1 to about 50 mN·m−1 at 37° C. In some embodiments, thecomposition has a surface tension of about 15 mN·m−1, about 20 mN·m−1,about 30 mN·m−1, about 36 mN·m−1, about 41 mN·m−1, about 48 mN·m−1,about 54 mN·m−1, about 75 mN·m−1, about 40 mN·m−1, about 50 mN·m−1,about 60 mN·m−1, about 70 mN·m−1, about 80 mN·m−1, or a range betweenany two of these values at 37° C. In some embodiments, the compositionhas a surface tension of about 42 mN·m−1 to about 55 mN·m−1 at 37° C. Insome embodiments, the composition has a surface tension of about 42mN·m−1 to about 50 mN·m−1 at 37° C.

In some embodiments, a composition comprising 40% hydrogen peroxide hasa surface tension of from about 35 mN·m−1 to about 60.3 mN·m−1 at 37° C.In some embodiments, a composition comprising 40% hydrogen peroxide mayhave a surface tension of about 60.3 mN·m−1 at 37° C. A compositioncomprising 40% hydrogen peroxide and 2.5% 2-propanol may have a surfacetension of about 54.1+/−0.8 mN·m−1 at 37° C. A composition comprising40% hydrogen peroxide and 5% 2-propanol may have a surface tension ofabout 48.3+/−0.7 mN·m−1 at 37° C. A composition comprising 40% hydrogenperoxide and 10% 2-propanol may have a surface tension of about41.1+/−0.6 mN·m−1 at 37° C. A composition comprising 40% hydrogenperoxide and 15% 2-propanol may have a surface tension of about35.9+/−0.6 mN·m−1 at 37° C.

In some embodiments, the composition has a pH of about 1.5 to about 7.0.In some embodiments, the pH may be about 1.5 to about 3.5, about 1.5 toabout 5.0, about 1.5 to about 4.0, about 1.7 to about 3.7, about 2.0 toabout 5.0, about 2.0 to about 4.0, about 2.0 to about 2.8, about 2.5 toabout 4.0, about 2.5 to about 4.5, about 2.5 to about 5.0, about 2.7 toabout 3.83, about 2.7 to about 4.0, about 2.8 to about 4.0, about 2.83to about 3.83, about 3.0 to about 7.0, about 4.0 to about 7.0, about 5.0to about 7.0, or about 6.0 to about 7.0. In some embodiments, the pH maybe about 1.5, 1.7, 2.0, 2.5, 2.7, 2.8, 2.83, 3.0, 3.3, 3.5, 3.7, 3.83,4.0, 4.5, 5.0, 5.5, 6.0, 6.5, 7.0, or a range between any two of thesevalues.

In some embodiments, the compositions of embodiments herein are stablefor up to about four weeks at room temperature. In some embodiments, thecompositions of embodiments herein are stable for up to about 15minutes, about 30 minutes, about 1 hour, about 2 hours, about 3 hours,about 4 hours, about 5 hours, about 6 hours, up to about 12 hours, up toabout 24 hours, up to about 1 week, up to about 2 weeks, up to about 3weeks, up to about 1 month, up to about 6 weeks, up to about 2 months,up to about 3 months, up to about 4 months, up to about 6 months, up toabout 8 months, up to about 10 months, up to about 12 months, up toabout 18 months, up to about 2 years, up to about 2.5 years, or up toabout 3 years at room temperature. In some embodiments, the compositionsof embodiments herein are stable for up to about four weeks, up to aboutsix weeks, up to about eight weeks, up to about three months, up toabout 6 months, up to about 8 months, or up to about a year at 40° C. Insome embodiments, the compositions of embodiments herein are stable forup to about four weeks, up to about 6 weeks, up to about 1 month, up toabout 2 months, up to about 3 months, up to about 4 months, up to about6 months, up to about 8 months, up to about 10 months, up to about 12months, up to about 18 months, up to about 2 years, up to about 2.5years, or up to about 3 years at 30° C. In some embodiments, thecompositions of embodiments herein are stable for up to about fourweeks, up to about 1 month, up to about 6 weeks, up to about 2 months,up to about 3 months, up to about 4 months, up to about 6 months, up toabout 8 months, up to about 10 months, up to about 12 months, up toabout 18 months, up to about 2 years, up to about 2.5 years, or up toabout 3 years at 25° C. In some embodiments, the compositions ofembodiments herein are stable for up to about four weeks, up to about 6weeks, up to about 1 month, up to about 2 months, up to about 3 months,up to about 4 months, up to about 6 months, up to about 8 months, up toabout 10 months, up to about 12 months, up to about 18 months, up toabout 2 years, up to about 2.5 years, or up to about 3 years at 5° C.

In some embodiments, the compositions of embodiments herein satisfy thestability requirements put forth by the International Conference ofHarmonisation of Technical Requirements for Registration ofPharmaceuticals for Human Use in the “ICH Harmonised TripartiteGuideline: Stability Testing of New Drug Substances and ProductsQ1A(R2)”, current Step 4 version, dated 6 Feb. 2003, the entirety ofwhich is incorporated herein by reference.

In some embodiments, the compositions of embodiments herein may also beadministered in combination with other methods that mechanically,physically or chemically enhance the penetration of the active into thelesion. Such methods may include tape-stripping, destructive/ablativemodalities such as, e.g., liquid nitrogen cryotherapy,electrodesiccation, lasers of various wavelengths (ablative andnon-ablative), radio-frequency ablation, dermabrasion, and partial orcomplete surgical removal by curettage or surgical excision, use of anablative or chemical peeling agent, or otherwise disturbing the surfaceof, or decreasing the thickness or size or overall volume of, orincreasing the surface area of the lesion. In some embodiments, thecompositions of embodiments herein may be administered in combinationwith other active ingredients, such as, for example, adjuvants,inhibitors, or other compatible drugs or compounds where suchcombination is seen to be desirable or advantageous in achieving thedesired effects of the methods described herein. Any other knowntreatment may be used in combination with the formulation to treat theskin diseases disclosed herein. For example, the composition may beadministered in combination with an active pharmaceutical agent that isused to treat the skin conditions described herein. In some embodiments,the compositions of embodiments herein may be administered before,concomitant with, or after the administration of another compound totreat the lesion. In some embodiments, the composition further comprisesa topically active pharmaceutical agent used to treat the skinconditions described herein. As an example, a method of treatingseborrheic keratosis may comprise administering ingenol mebutate to thesubject and then administering the compositions of embodiments herein.As another example, a method of treating warts may compriseadministering salicylic acid to the lesion of a person in need thereofin the morning and administering a composition of embodiments herein tothe lesion of a person in need thereof in the evening. As anotherexample, a method of treating warts, seborrheic keratosis, condylomaacuminate, mollusca, or acrochordons may comprise administering atopical retinoid to the lesion of a person in need thereof for a numberof days and administering a composition of embodiments herein to thelesion of a person in need thereof after a number of days ofpretreatment with the topical agent. Other possible examples will bereadily apparent to one knowledgeable in the art. The other active orprocedure may be administered or performed either before, after orconcurrently with the compositions of embodiments herein.

Embodiments herein are also directed to a method of treating a skincondition comprising administering a composition of embodiments hereinto a subject in need thereof. In some embodiments, the composition maybe administered once daily, twice daily, weekly, biweekly, three times aweek, every other day, monthly, every two months, every three months oras directed by the packaging or the physician to achieve the desiredclinical result. The skin condition may be of infectious etiology. Theskin condition may be a virally induced or non-virally induced cutaneousgrowth or proliferation. The skin condition may be a benign neoplasm,premalignancy or malignancy. The skin condition may be an inflammatorycondition. The skin condition may be a hyperproliferative condition. Theskin condition may be ageing including intrinsic and extrinsic changes(e.g., photoaging (ultraviolet light induced changes)), pigmentarychanges, fine lines and rhytides. In some embodiments, the skincondition may be selected from Human Papilloma Virus induced lesionse.g., warts, common warts, recurrent warts, recalcitrant warts,treatment naïve warts, palmoplantar warts, flat warts, epidermodysplasiaverruciformis related warts, anogenital warts, condyloma accuminatum,cervical dysplasias or neoplasias, e.g., cervical intraepithelialneoplasia (CIN); Herpesvirus related lesions including those induced byHHV-1 (HSV-1), HHV-2 (HSV-2), HHV-3 (varicella-zoster virus) e.g.,chicken pox, Herpes zoster, shingles; Poxvirus induced lesions e.g.,molluscum contagiosum, orf, callus, cutaneous horns, corns,acrochordons, fibroepithelial polyps, prurigo nodularis, actinickeratoses, squamous cell carcinoma, squamous cell carcinoma in situ,keratoacanthoma, basal cell carcinoma, cutaneous lymphomas and benignlymphocytic infiltrates & hyperplasias of the skin, clear cellacanthoma, large cell acanthoma, epidermolytic acanthoma, porokeratosis,hyperkeratosis, keratosis pilaris, lichenoid keratosis, acanthosis,acanthosis nigricans, confluent and reticulated papillomatosis, nevi,including e.g., dermal nevi, epidermal nevi, compound nevi, ILVEN(inflammatory linear verrucous epidermal nevi), nevus sebaceous, nevuscomedonicus, and the like; acne, e.g., comedonal acne, inflammatoryacne, papular acne, pustular acne, cystic acne; cysts, e.g., epidermoidcysts, milia, trichilemmal cysts, follicular cysts, proliferating cysts,dermoid cysts, pilonidal cysts, apocrine cysts, eccrine cysts, sebaceouscysts, mucous cysts, myxoid cysts, ganglion cysts, synovial cysts,vellus hair cysts, steatocystoma, hidrocystoma; adnexal neoplasms e.g.,trichofolliculoma, fibrofolliculoma, perifollicular fibroma,trichodiscoma, nevus sebaceous, chondroid syringoma, trichoepithelioma,trichoblastoma, desmoplastic trichoepithelioma, pilomatricoma,pilomatrical carcinoma, tricholemmoma, trichelemmal carcinoma, tumor ofthe follicular infundibulum, tricoadenoma, proliferating pilar tumor,sebaceous hyperplasia, sebaceous adenoma, sebaceous epithelioma,sebaceous carcinoma, syringoma, poroma, hidradenoma, apocrinehidradenoma, spiradenoma, cylindroma, eccrine nevus (eccrine hamartoma),papillary adenoma, papillary adenocarcinoma; benign melanocyticproliferations or neoplasms e.g., ephilides, café-au-lait macules,Becker's melanosis, lentigines, solar lentigines, lentigo simplex,mucosal melanocytic lesions, Mongolian spots, Nevus of Ota, blue nevus,common acquired melanocytic nevi (nevocellular nevus, “moles”),congenital nevi, nevus spilus, recurrent nevi; vascular and perivascularneoplasms and reactive hyperplasias e.g., hemangiomas, cherry angiomas,hobnail hemangiomas (targeted hemosiderotic hemangiomas), tuftedangiomas, hemangioendotheliomas, angiolymphoid hyperplasia witheosinophilia (ALHE), Glomus tumors (glomangiomas), hemangiopericytomas;cutaneous neural and neuroendocrine neoplasms e.g., neuromas,Schwannomas, neurofibromas, nerve sheath tumor, nerve sheath myxoma,neurothekeoma, granular cell tumor; fibrotic and fibrohistiocyticproliferations e.g., acrochordons, fibroepithelial polyps, fibromas,fibrous papules, angiofibromas, pearly penile papules, periungualfibromas, dermatofibromas, fibrokeratomas, sclerotic or pleomorphicfibromas, connective tissue nevi; cutaneous scars, hyperplasias,keloids, rosacea, cutaneous fungal, dermatophyte & mold infections,onychomycosis, hyperpigmentation, psoriasis, malignant melanoma,seborrheic keratosis, seborrheic keratosis variants including e.g.,dermatosis papulosis nigra, inverted follicular keratosis/keratoma wartydyskeratosis/warty dyskeratoma, acrokeratosis verruciformis, stuccokeratosis; or a combination thereof.

In some embodiments, the method of treating a skin condition furthercomprises the step of cleansing the treatment site before administrationof the composition. In some embodiments, cleansing the treatment sitecomprises defatting the treatment site before the administration of thecomposition. In some embodiments cleansing the treatment site comprisesapplying at least 70% 2-propanol to the skin to be treated beforeadministration of the composition. Defatting the treatment site maycomprise applying the alcohol onto the skin, such as by rubbing,massaging, placing, scrubbing, abrading, wiping, swabbing, or otherwisecontacting the skin with the alcohol.

In some embodiments, the method of treating a skin condition furthercomprises the step of debriding the treatment site of the subject. Insome embodiments, debriding may include mechanically, chemically, orphysically abrading, ablating, thinning, curetting, destroying,removing, excising, or otherwise disturb the surface of the skin orlesion to be treated, including decreasing the thickness of, and/ordecreasing the volume of the lesion. In some embodiments, the step ofdebriding is before, after, and/or concurrent with administration of thecompositions of embodiments herein to the treatment site.

In some embodiments, the alcohol may be selected from a primary alcohol,a secondary alcohol, a tertiary alcohol, or a combination thereof. Thealcohol may be selected from methanol, ethanol, butanol, 1-propanol,pentanol, hexanol, octanol, nonanol, decanol, 2-butanol, 2-propanol,2-pentanol, 2-hexanol, benzyl alcohol, an isomer thereof, or acombination thereof. In some embodiments, defatting the skin maycomprise applying another known defatting agent to the skin such asethyl acetate, butyl acetate, or the like onto the skin, such as byrubbing, massaging, placing, scrubbing, abrading, wiping, swabbing, orotherwise contacting the skin with the agent. In some embodiments,cleansing the skin comprises applying an antiseptic solution to the skinor skin lesion to be treated. In some embodiments, the antiseptic ispovidone, iodine, chlorhexidine, a detergent, soap or the like.

Some embodiments are directed to a method of treating warts comprisingadministering a composition of embodiments herein to a subject in needthereof. In some embodiments, the composition comprises an alcohol andup to about 50% hydrogen peroxide. In some embodiments, warts may betreated using any of the methods of treatment described herein. Someembodiments are directed to a method of improving the appearance ofwarts comprising administering a composition of embodiments herein to asubject in need thereof. Some embodiments are directed to a method ofimproving the appearance of warts comprising administering a compositionof embodiments herein to a subject in need thereof. Some embodiments aredirected to a method of alleviating, e.g., shrinking, reducing in size,and/or reducing in height, a wart comprising administering a compositionof embodiments herein to a subject in need thereof. In some embodiments,the warts are treatment naïve. In some embodiments, a treatment naïvewart may be treated using any of the methods of treatment describedherein. Some embodiments are directed to a method of improving theappearance of treatment naïve warts comprising administering acomposition of embodiments herein to a subject in need thereof. Someembodiments are directed to a method of improving the appearance oftreatment naïve warts comprising administering a composition ofembodiments herein to a subject in need thereof. Some embodiments aredirected to a method of alleviating, e.g., shrinking, reducing in size,and/or reducing in height, a treatment naïve wart comprisingadministering a composition of embodiments herein to a subject in needthereof. In some embodiments, the warts are recalcitrant warts.Recalcitrant warts may include warts that are resistant to or havefailed or have partially responded to other therapies, warts that aredifficult to treat, or warts that are in anatomically difficultlocations. In some embodiments, recalcitrant warts may include plantarwarts, periungal warts, subungal warts or the like. In some embodiments,recalcitrant warts may be located on any body surface. In someembodiments, recalcitrant warts may be treated using any of the methodsof treatment described herein. Some embodiments are directed to a methodof improving the appearance of recalcitrant warts comprisingadministering a composition of embodiments herein to a subject in needthereof. Some embodiments are directed to a method of improving theappearance of recalcitrant warts comprising administering a compositionof embodiments herein to a subject in need thereof. Some embodiments aredirected to a method of alleviating, e.g., shrinking, reducing in size,and/or reducing in height, a recalcitrant wart comprising administeringa composition of embodiments herein to a subject in need thereof. Insome embodiments, the composition comprises about 25% hydrogen peroxideand 5% 2-propanol. In some embodiments, the composition comprises about32.5% hydrogen peroxide and 5% 2-propanol. In some embodiments, thecomposition comprises about 40% hydrogen peroxide and 5% 2-propanol. Insome embodiments, the composition comprises about 45% hydrogen peroxideand 5% 2-propanol. In some embodiments, the composition comprises up toabout 50% hydrogen peroxide and 2-propanol.

Some embodiments are directed to a method of treating seborrheickeratosis comprising administering a composition of embodiments hereinto a subject in need thereof. In some embodiments, the compositioncomprises an alcohol and up to about 50% hydrogen peroxide. In someembodiments, the composition comprises about 45% hydrogen peroxide and5% 2-propanol. In some embodiments, the composition comprises about 40%hydrogen peroxide and 5% 2-propanol. In some embodiments, thecomposition comprises about 35% hydrogen peroxide and about 5%2-propanol. In some embodiments, the composition comprises about 32.5%hydrogen peroxide and about 5% 2-propanol. In some embodiments, thecomposition comprises about 25% hydrogen peroxide and about 5%2-propanol.

Some embodiments are directed to a method of treating acrochordonscomprising administering a composition of embodiments herein to asubject in need thereof. In some embodiments, the composition comprisesan alcohol and up to about 50% hydrogen peroxide. In some embodiments,the composition comprises about 45% hydrogen peroxide and 5% 2-propanol.In some embodiments, the composition comprises about 40% hydrogenperoxide and 5% 2-propanol. In some embodiments, the compositioncomprises about 35% hydrogen peroxide and about 5% 2-propanol. In someembodiments, the composition comprises about 32.5% hydrogen peroxide andabout 5% 2-propanol. In some embodiments, the composition comprisesabout 25% hydrogen peroxide and about 5% 2-propanol.

Some embodiments herein are directed to a method of treating a skincondition comprising (i) topically administering a first dose of acomposition comprising up to about 50% hydrogen peroxide and an alcohol;and (ii) topically administering one or more follow-up doses of thecomposition. In some embodiments, the application of the first dose andone or more follow-up doses comprises one application session. In someembodiments, the follow-up dose is administered immediately afteradministration of the first dose. In some embodiments, the follow-updose is administered at least about 0.5 minutes after the first dose. Insome embodiments, the follow-up dose is administered at least about 1minute, at least about 1.5 minutes, at least about 2 minutes, at leastabout 5 minutes, at least about 10 minutes, at least about 15 minutes,at least about 20 minutes, at least about 25 minutes, at least about 30minutes, or at least about 1 hour after the first dose. In someembodiments, there may be one follow-up dose, two follow-up doses, threefollow-up doses, four follow-up doses, five follow-up doses, sixfollow-up doses, seven follow-up doses, eight follow-up doses, ninefollow-up doses or ten follow-up doses in each application session. Eachsubsequent follow-up dose may be administered immediately afteradministration of the previous dose, at least about 1 minute, at leastabout 1.5 minutes, at least about 2 minutes, at least about 5 minutes,at least about 10 minutes, at least about 15 minutes, at least about 20minutes, at least about 25 minutes, at least about 30 minutes or atleast one hour after the previous dose.

In some embodiments, the topical composition may be administered in aneffective dose. In some embodiments, an effective dose may be from about0.0025 milliliters to about 3 milliliters of the compositions ofembodiments herein, including about 0.0025 milliliters, about 0.01milliliters, about 0.025 milliliters, about 0.05 milliliters, about0.075 milliliters, about 0.1 milliliters, about 0.15 milliliters, about0.5 milliliters, about 1 milliliters, about 1.5 milliliters, about 2millimeters, about 2.5 milliliters, about 3 milliliters, a combinationthereof, or any amount that has a clinical effect on the lesion. In someembodiments, the effective dose is proportional to size of the lesion.In some embodiments, the effective dose of the composition is less thanabout 0.1 milliliters per lesion. In some embodiments, an effective dosemay be about 3 milliliters of the compositions of embodiments herein. Insome embodiments, an effective dose may be from about 2 milliliters toabout 3 milliliters of the compositions of embodiments herein. In someembodiments, an effective dose may be from about 2 milliliters to about5 milliliters of the compositions of embodiments herein.

In some embodiments, topical administration of the first dose and thefollow-up doses comprises massaging the composition into the skin for atleast about 5 seconds, at least about 10 seconds, at least about 15seconds, at least about 20 seconds, at least about 25 seconds, at leastabout 30 seconds, at least about 35 seconds, at least about 40 seconds,at least about 45 seconds, at least about 50 seconds, at least about 55seconds, at least about 1 minute, at least about 2 minutes, at leastabout 3 minutes, at least about 4 minutes, or at least about 5 minutes,at least about 10 minutes, at least about 15 minutes, at least about 20minutes at least about 25 minutes, or at least about 30 minutes duringeach dose. In some embodiments, the composition is a solution. In someembodiments, the composition is a gel. In some embodiments, massagingincludes rubbing-in, manipulating, kneading, pressing, or otherwise“working” the composition into the skin. In some embodiments, thecomposition is applied and massaged into the skin with an applicator. Insome embodiments, the composition is applied and massaged into the skinat least 1 time, at least 2 times, at least 3 times, at least 4 times,at least 5 times, at least 6 times, at least 7 times, at least 8 times,at least 9 times, or at least 10 times in each application session. Insome embodiments, the application session, in which the composition isadministered, may be repeated once daily, twice daily, weekly, biweekly,three times a week, every other day, monthly, every two months, everythree months, every six months or as directed by the packaging or thephysician to achieve the desired clinical result.

In some embodiments, the composition is administered by a health careprovider. In some embodiments, the composition is administered in ahealth care setting. In some embodiments, the composition isself-administered by the subject in need thereof. In some embodiments,the composition is administered by a caregiver of the subject. As usedherein, health care provider may include doctor, nurse, physician'sassistant, nurse practitioner, medical assistant, or any professionalworking in a doctor's office, hospital or clinic. A health care setting,as used herein, refers to a doctor's office, hospital, ambulatory caresetting, or clinic. A caregiver of the subject may include parents,nurse, friend, family member, medical professional, or anybody assistingin administering the composition to the subject in need thereof.

In some embodiments, the method further comprises topicallyadministering a second composition comprising hydrogen peroxide andalcohol as described in embodiments above to the subject following aninitial treatment by a health care provider. In some embodiments, thesecond composition is a take home composition. In some embodiments, thesecond composition is available over the counter. In some embodiments,the second composition is available by prescription. In someembodiments, the second composition may comprise a lower concentrationof hydrogen peroxide than the initial treatment administered to thesubject. In some embodiments, the second composition may comprise thesame concentration of hydrogen peroxide as the initial treatmentadministered to the subject. In some embodiments, the second compositioncomprises up to about 50% hydrogen peroxide and an alcohol. In someembodiments, the second composition comprises about 45% hydrogenperoxide and 5% alcohol. In some embodiments, the second compositioncomprises about 40% hydrogen peroxide and 5% alcohol. In someembodiments, the second composition comprises about 35% hydrogenperoxide and 5% alcohol. In some embodiments, the second compositioncomprises about 32.5% hydrogen peroxide and 5% alcohol. In someembodiments, the second composition comprises about 25% hydrogenperoxide and 5% alcohol. In some embodiments, the alcohol is 2-propanol.In some embodiments, the second composition may be self-administered bythe subject. In some embodiments, the second composition may beadministered at least about 1 day, at least about 2 days, at least about3 days, at least about 1 week, at least about 2 weeks, at least about 3weeks, at least about 4 weeks, at least about 5 weeks, at least about 6weeks, at least about 7 weeks or at an interval required to maintain theclinical effect or until the lesion is cleared, after the initialtreatment by the healthcare professional. In some embodiments, thesecond composition may be administered once daily, twice daily, weekly,biweekly, every other day, monthly, every two months, every threemonths, every six months, or as directed by the packaging or thephysician to achieve the clinically desired result.

Some embodiments herein are directed to a method of treating a skincondition in a subject comprising topically administering a take homecomposition comprising hydrogen peroxide and alcohol as described aboveto the subject. In some embodiments, the take home composition isavailable over the counter. In some embodiments, the take homecomposition is available by prescription. In some embodiments, the takehome composition comprises about 50% hydrogen peroxide and an alcohol.In some embodiments, the take home composition comprises about 45%hydrogen peroxide and 5% alcohol. In some embodiments, the take homecomposition comprises about 40% hydrogen peroxide and 5% alcohol. Insome embodiments, the take home composition comprises about 35% hydrogenperoxide and 5% alcohol. In some embodiments, the take home compositioncomprises about 32.5% hydrogen peroxide and 5% alcohol. In someembodiments, the take home composition comprises about 25% hydrogenperoxide and 5% alcohol. In some embodiments, the alcohol is 2-propanol.Such take home compositions may be administered following a visit to ahealthcare professional. In some embodiments, the take home compositionmay be administered following an initial treatment by a healthcareprofessional. In some embodiments, the take home composition maycomprise a lower concentration of hydrogen peroxide than the initialtreatment administered to the subject. In some embodiments, the takehome composition may comprise the same concentration of hydrogenperoxide as the initial treatment administered to the subject. The takehome composition may be self-administered by the subject. In someembodiments, the take home composition may be administered at leastabout 1 day, at least about 2 days, at least about 3 days, at leastabout 1 week, at least about 2 weeks, at least about 3 weeks, at leastabout 4 weeks after the initial treatment by the healthcareprofessional. In some embodiments, the take home composition may beadministered once daily, twice daily, weekly, biweekly, every other day,monthly, every two months, every three months, every six months, or asdirected by the packaging or the physician to achieve the clinicallydesired result.

Embodiments herein also encompass devices for administering the hydrogenperoxide compositions of embodiments herein (see, for example, FIGS.12-16 and associated description). In some embodiments, a compositioncomprising hydrogen peroxide and alcohol as described in embodimentsherein may be administered using any topical applicator known in theart. In some embodiments, a composition comprising hydrogen peroxide andalcohol as described in embodiments herein may be administered using asponge, a swab, a foam tipped stick, a cotton ball, a brush, a woven ornon-woven fabric, roller, gauze, a pen, a glove, or the like. In someembodiments, the applicator may dispense compositions of embodimentsherein via a tip that is flocked, absorbent, and/or firm enough to applypressure to the lesion. In some embodiments the applicator is a sinteredpolymeric-tip applicator. In some embodiments, the applicator isresistant to, compatible with, or inert to high concentration peroxidesolutions. In some embodiments, the applicator is capable of dispensingthe solution at a controlled rate in order to help confine the active tothe lesion of interest and spare surrounding normal skin. In someembodiments, the solution may be administered using a device having thehydrogen peroxide solution in a compartment that dispenses the solutiononto or through an applicator tip when needed. In some embodiments, theapplicator may comprise a material designed to abrade the skin lesion ortreatment site before, after, or at the time of administration of thecomposition. In some embodiments, the applicator is a doe footedapplicator. In some embodiments, the applicator is a flocked, doe footedapplicator. In some embodiments, the flocked, doe footed applicator iscomprised of HDPE (high density polyethylene), nylon, and an adhesive.In some embodiments, the solution is applied once daily, twice daily,weekly, biweekly, three times a week, every other day, monthly, everytwo months, every three months or as directed by the packaging or thephysician or provider to achieve the desired clinical result.

In some embodiments, a method of treating a skin condition comprisesadministering the composition of embodiments herein. In someembodiments, administering the composition of embodiments hereincomprises contacting a treatment site with a tip of an applicator,wherein the applicator comprises a frangible ampoule having thecomposition disposed therein, an applicator body having the frangibleampoule arranged therein, an applicator hub in fluid communication withthe applicator body, the tip arranged at a proximal end of theapplicator hub, and a filter arranged between the frangible ampoule andthe tip. In some embodiments, administering the topical compositioncomprises controlling a flow rate of the topical composition out of thetip by varying a squeezing force applied to the exterior surface of theapplicator body. In some embodiments, administering the topicalcomposition comprises contacting the tip with a targeted lesion of theskin condition whereby the topical composition dispenses through the tiponto the targeted lesion. In some embodiments, administering the topicalcomposition further comprises applying pressure to a pressure areaarranged on an outer surface of the applicator body causing thefrangible ampoule to rupture. In some embodiments, administering thetopical composition comprises causing the frangible ampoule to ruptureand release the topical composition through the tip; and contacting thetip to a targeted lesion of the skin condition.

Some embodiments herein are directed to a kit for the treatment of askin condition comprising a container comprising a compartment havinghydrogen peroxide, a compartment having 2-propanol and instructions foruse. Some embodiments are directed to a kit for the treatment of a skincondition comprising a container comprising hydrogen peroxide and2-propanol and instructions for use. In some embodiments, the kitfurther comprises an applicator. In some embodiments, the kit mayinclude two or more applicators. For example, in some embodiments, a kitmay contain many applicators where there is more than one lesion totreat (for example, in an over the counter kit or a kit for multipleadministrations by the physician) or if the kit further includes a takehome formulation of the composition for multiple applications. In someembodiments, the kit may comprise an applicator with a frangible glassampoule having a solution of hydrogen peroxide and an alcohol. In someembodiments, the kit may comprise an applicator with a frangible glassampoule having a solution of hydrogen peroxide, wherein the applicatoralso comprises a compartment having an alcohol, such as, withoutlimitation, 2-propanol, in the applicator body. In some embodiments, theapplicator may further include a compartment having a gelling agent. Insome embodiments, the kit may comprise two or more containers of thetopical hydrogen peroxide formulation. In some embodiments, the two ormore containers of the topical hydrogen peroxide formulation maycomprise hydrogen peroxide formulations of the same hydrogen peroxideconcentration. In some embodiments, the two or more containers of thetopical hydrogen peroxide formulation may comprise hydrogen peroxideformulations of different hydrogen peroxide concentrations. For example,in some embodiments, the kit may comprise one 40% hydrogen peroxide and5% 2-propanol container for administration by the physician in theoffice, and other containers of different concentrations (e.g., weakerconcentrations) of hydrogen peroxide for the patient to take home forsubsequent applications to the target site. In some embodiments, a kitmay include two or more single-use containers of the topical hydrogenperoxide formulation with multiple applicators. In some embodiments, akit may include a container having multiple dose containers of thetopical hydrogen peroxide formulation with multiple applicators. Theskin condition may be a virally induced or non-virally induced cutaneousgrowth or proliferation. The skin condition may be a benign neoplasm,premalignancy or malignancy. The skin condition may be an inflammatorycondition. The skin condition may be a hyperproliferative condition. Theskin condition may be ageing including intrinsic and extrinsic changes(e.g., photoaging (ultraviolet light induced changes)), pigmentarychanges, fine lines and rhytides. In some embodiments, the skincondition may be selected from Human Papilloma Virus induced lesionse.g., warts, common warts, palmoplantar warts, flat warts, recurrentwarts, recalcitrant warts, treatment naïve warts, epidermodysplasiaverruciformis related warts, anogenital warts, condyloma accuminatum,cervical dysplasias or neoplasias, e.g., cervical intraepithelialneoplasia (CIN); Herpesvirus related lesions including those induced byHHV-1 (HSV-1), HHV-2 (HSV-2), HHV-3 (varicella-zoster virus) e.g.,chicken pox, Herpes zoster, shingles; Poxvirus induced lesions e.g.,molluscum contagiosum, orf, callus, cutaneous horns, corns,acrochordons, fibroepithelial polyps, prurigo nodularis, actinickeratoses, squamous cell carcinoma, squamous cell carcinoma in situ,keratoacanthoma, basal cell carcinoma, cutaneous lymphomas and benignlymphocytic infiltrates & hyperplasias of the skin, clear cellacanthoma, large cell acanthoma, epidermolytic acanthoma, porokeratosis,hyperkeratosis, keratosis pilaris, lichenoid keratosis, acanthosis,acanthosis nigricans, confluent and reticulated papillomatosis, nevi,including e.g., dermal nevi, epidermal nevi, compound nevi, ILVEN(inflammatory linear verrucous epidermal nevi), nevus sebaceous, nevuscomedonicus, and the like; acne, e.g., comedonal acne, inflammatoryacne, papular acne, pustular acne, cystic acne; cysts, e.g., epidermoidcysts, milia, trichilemmal cysts, follicular cysts, proliferating cysts,dermoid cysts, pilonidal cysts, apocrine cysts, eccrine cysts, sebaceouscysts, mucous cysts, myxoid cysts, ganglion cysts, synovial cysts,vellus hair cysts, steatocystoma, hidrocystoma; adnexal neoplasms e.g.,trichofolliculoma, fibrofolliculoma, perifollicular fibroma,trichodiscoma, nevus sebaceous, chondroid syringoma, trichoepithelioma,trichoblastoma, desmoplastic trichoepithelioma, pilomatricoma,pilomatrical carcinoma, tricholemmoma, trichelemmal carcinoma, tumor ofthe follicular infundibulum, tricoadenoma, proliferating pilar tumor,sebaceous hyperplasia, sebaceous adenoma, sebaceous epithelioma,sebaceous carcinoma, syringoma, poroma, hidradenoma, apocrinehidradenoma, spiradenoma, cylindroma, eccrine nevus (eccrine hamartoma),papillary adenoma, papillary adenocarcinoma; benign melanocyticproliferations or neoplasms e.g., ephilides, café-au-lait macules,Becker's melanosis, lentigines, solar lentigines, lentigo simplex,mucosal melanocytic lesions, Mongolian spots, Nevus of Ota, blue nevus,common acquired melanocytic nevi (nevocellular nevus, “moles”),congenital nevi, nevus spilus, recurrent nevi; vascular and perivascularneoplasms and reactive hyperplasias e.g., hemangiomas, cherry angiomas,hobnail hemangiomas (targeted hemosiderotic hemangiomas), tuftedangiomas, hemangioendotheliomas, angiolymphoid hyperplasia witheosinophilia (ALHE), Glomus tumors (glomangiomas), hemangiopericytomas;cutaneous neural and neuroendocrine neoplasms e.g., neuromas,Schwannomas, neurofibromas, nerve sheath tumor, nerve sheath myxoma,neurothekeoma, granular cell tumor; fibrotic and fibrohistiocyticproliferations e.g., acrochordons, fibroepithelial polyps, fibromas,fibrous papules, angiofibromas, pearly penile papules, periungualfibromas, dermatofibromas, fibrokeratomas, sclerotic or pleomorphicfibromas, connective tissue nevi; cutaneous scars, hyperplasias,keloids, rosacea, cutaneous fungal, dermatophyte & mold infections,onychomycosis, hyperpigmentation, rhytides, psoriasis, malignantmelanoma, seborrheic keratosis, seborrheic keratosis variants includinge.g., dermatosis papulosis nigra, inverted follicular keratosis/keratomawarty dyskeratosis/warty dyskeratoma, acrokeratosis verruciformis,stucco keratosis; or a combination thereof. In some embodiments, theapplicator may be selected from a sponge, a swab, a foam tipped stick, acotton ball, a brush, a woven or non-woven fabric, roller, gauze, a pen,or the like. In some embodiments, the applicator is flocked, absorbent,and/or firm enough to apply pressure to the lesion. In some embodimentsthe applicator is a sintered polymeric-tip applicator. In someembodiments, the applicator is resistant to, compatible with, or inertto high concentration peroxide solutions. In some embodiments, theapplicator is capable of dispensing the solution at a controlled rate inorder to help confine the active to the lesion of interest and sparesurrounding normal skin. In some embodiments, the solution may beadministered using a device having the hydrogen peroxide solution in acompartment that dispenses the solution onto or through an applicatortip when needed. In some embodiments, the applicator may comprise amaterial designed to abrade the skin lesion or treatment site before orat the time of administration of the composition. In some embodiments,the applicator is a doe footed applicator. In some embodiments, theapplicator is a flocked, doe footed applicator. In some embodiments, theflocked, doe footed applicator is comprised of HDPE (high densitypolyethylene), LDPE (low density polyethylene), Nylon, an adhesive, orany combination thereof. In some embodiments, the container may beselected from a vial, an ampule, a jar, a bottle, a medication tube, asyringe, or any other container for storing liquids. In someembodiments, the compartment may be selected from a vial, a tube, anampoule, a jar, a bottle, a medication tube, a syringe, or any othercontainer for storing liquids. In some embodiments the container may beglass, borosilicate glass, Type I borosilicate glass, tinted orotherwise light protected glass, amber tinted glass, amber Type Iborosilicate glass, HDPE, Teflon®, silicone, ABS (acrylonitrilebutadienestylene), or other compatible polymer or material. In some embodiments,the kit may include a glass vial or bottle having a solution of hydrogenperoxide and an alcohol disposed therein. In some embodiments the glassvial or bottle may include an amber glass vial or bottle. In someembodiments, the kit may comprise a vial or bottle at least partiallyformed from HDPE having a solution of hydrogen peroxide and an alcoholdisposed therein. In some embodiments, the container may be formed froma material that has a low reactivity with peroxide. In some embodiments,the compartment may include a material that has a low reactivity withperoxide. In some embodiments, the hydrogen peroxide is a stabilizedhydrogen peroxide. In some embodiments, the alcohol, such as, withoutlimitation, 2-propanol, is in an amount of less than about 25%. In someembodiments, the kit may be for use by a health care provider. In someembodiments, the kit may be for use by the subject in need thereof. Insome embodiments, the kit may be available only with a prescription. Insome embodiments, the kit may be available over the counter for use bythe subject in need thereof.

FIG. 12 depicts an illustrative applicator configured according to afirst embodiment. As shown in FIG. 12, the applicator 1200 may includean applicator body 1205. In some embodiments, the applicator tube 1205may be enclosed at a distal end thereof by an end cap 1215. In someembodiments, the applicator body 1205 and/or the end cap 1215 may beformed from various flexible materials, including, without limitation,flexible polymer materials. Non-limiting examples of flexible polymermaterials may include polypropylene (PP), high-density polyethylene(HDPE) or low-density polyethylene (LDPE), polyvinyl chloride (PVC),polyethylene (PE), derivatives thereof, and any combination thereof. Insome embodiments, the applicator body 1205 may have a generallylongitudinal shape. In some embodiments, the applicator body 1205 mayhave a generally cylindrical shape. The applicator body 1205 may havevarious lengths according to some embodiments, including about 80millimeters, about 90 millimeters, about 98 millimeters, about 99millimeters, about 100 millimeters, about 110 millimeters, about 120millimeters, about 130 millimeters, about 140 millimeters, about 150millimeters, about 80 millimeters to about 100 millimeters, about 80millimeters to about 150 millimeters, about 90 millimeters to about 100millimeters, about 100 millimeters to about 120 millimeters, about 100millimeters to about 150 millimeters, and any values or ranges betweenany of these values (including endpoints). The applicator body 1205 mayhave various outer dimensions according to some embodiments, includingabout 5 millimeters, about 7 millimeters, about 9 millimeters, about 10millimeters, about 12 millimeters, about 15 millimeters, about 18millimeters, about 20 millimeters, about 5 millimeters to about 7millimeters, about 5 millimeters to about 10 millimeters, about 7millimeters to about 10 millimeters, about 9 millimeters to about 15millimeters, about 10 millimeters to about 15 millimeters, about 5millimeters to about 20 millimeters, about 10 millimeters to about 20millimeters, and any values or ranges between any of these values(including endpoints).

In some embodiments, an ampoule 1210 configured to store compositions ofembodiments herein may be arranged within a cavity formed within theapplicator body 1205. In some embodiments, the ampoule 1210 may befrangible, for example, configured to shatter, fragment, rupture,fracture, or otherwise break apart responsive to the application ofsufficient pressure thereto. For instance, sufficient pressure may beapplied manually, such as by applying a force by a human hand (forexample, by squeezing or pressing) on the applicator body 1205 in adirection toward the ampoule 1210 in an area of the applicator bodywhere the ampoule is located. In this manner, the force applied to theapplicator body 1205 may be transferred to the ampoule 1210 and theampoule may break apart responsive to the application of sufficientforce thereto. In some embodiments, the ampoule 1210 may be formed fromvarious frangible materials, including glass, plastic, a polymermaterial, borosilicate glass, Type I borosilicate glass, tinted glass,and any combination thereof. In some embodiments, the ampoule 1210 mayinclude one or more weakened regions to facilitate breakage of theampoule 1210. In some embodiments, the compositions of embodimentsherein may be caustic and/or may react with the materials of theapplicator 1200 or the environment. In some embodiments, thecompositions of embodiments herein may be degraded or otherwise effectedby contaminants and/or contact with the environment. Accordingly,storage of compositions of embodiments herein using one or more ampoules1210 may protect the applicator 1200 materials and/or the compositionsof embodiments herein from being degraded until they are released fromthe ampoule. Through the use of the ampoules 1210, the applicator 1200may, among other things, allow for the safe and stable storage ofcompositions of embodiments herein and other components until deliveryis required.

The compositions of embodiments herein stored within the ampoule 1210may be released within the applicator body 1205 responsive to thefracturing of the ampoule 1210. The ampoule 1210 may be configured tohold various volumes of the compositions of embodiments herein,including, about 0.1 milliliters, about 0.2 milliliters, about 0.5milliliters, about 1 milliliters, about 1.5 milliliters, about 2milliliters, about 2.4 milliliters, about 3 milliliters, about 3.2milliliters, about 4 milliliters, about 5 milliliters, about 10milliliters, about 20 milliliters, about 30 milliliters, about 50milliliters, about 100 milliliters, about 500 milliliters, about 0.1milliliters to about 3 milliliters, about 0.1 milliliters to about 4milliliters, about 0.1 milliliters to about 5 milliliters, about 0.1milliliters to about 10 milliliters, about 0.1 milliliters to about 100milliliters, about 0.1 milliliters to about 500 milliliters, about 1milliliters to about 3 milliliters, about 1 milliliters to about 4milliliters, about 1 milliliters to about 5 milliliters, about 1milliliters to about 100 milliliters, about 1 milliliters to about 500milliliters, about 2 milliliters to about 3 milliliters, about 2milliliters to about 4 milliliters, about 2 milliliters to about 5milliliters, about 2 milliliters to about 10 milliliters, about 3milliliters to about 4 milliliters, about 3 milliliters to about 5milliliters, about 3 milliliters to about 10 milliliters, about 3milliliters to about 100 milliliters, about 4 milliliters to about 5milliliters, about 4 milliliters to about 10 milliliters, about 4milliliters to about 100 milliliters, about 5 milliliters to about 10milliliters, about 5 milliliters to about 100 milliliters, about 100milliliters to about 500 milliliters, and any values or ranges betweenany of these values (including endpoints). In some embodiments, theampoule 1210 may be configured to hold an effective dose of thecompositions of embodiments herein. In some embodiments, the ampoule1210 may be configured to hold an effective dose of the compositions ofembodiments herein sufficient to treat a single target lesion or skinarea. In some embodiments, the ampoule 1210 may be configured to hold aneffective dose of the compositions of embodiments herein sufficient totreat multiple target lesions or skin areas. In some embodiments, aneffective dose may be from about 0.0025 milliliters to about 3milliliters of the compositions of embodiments herein, including about0.0025 milliliters, about 0.01 milliliters, about 0.025 milliliters,about 0.05 milliliters, about 0.075 milliliters, about 0.1 milliliters,about 0.15 milliliters, about 0.5 milliliters, about 1 milliliters,about 1.5 milliliters, about 2 millimeters, about 2.5 milliliters, about3 milliliters, a combination thereof, or any amount that has a clinicaleffect on the lesion. In some embodiments, the effective dose isproportional to size of the lesion. In some embodiments, the effectivedose of the composition is less than about 0.1 milliliters per lesion.In some embodiments, an effective dose may be about 3 milliliters of thecompositions of embodiments herein. In some embodiments, an effectivedose may be from about 2 milliliters to about 3 milliliters of thecompositions of embodiments herein. In some embodiments, an effectivedose may be from about 2 milliliters to about 5 milliliters of thecompositions of embodiments herein.

Although only one ampoule 1210 is depicted in FIG. 12, embodiments arenot so limited, as the applicator 1200 may include a plurality ofampoules. For instance, an applicator 1200 may include multiple ampoules1210 for multiple doses of the compositions of embodiments herein. Inanother instance, an applicator 1200 may include a plurality of ampoules1210 housing different compositions. In some embodiments, the applicator1200 may include a compartment (not shown) housing a first composition(e.g., a gelling agent, hydrogen peroxide) and one or more ampoules 1210housing one or more second compositions (e.g., 2-propanol, compositionsof embodiments herein). For example, one or more walls may partition theapplicator body into one or more compartment portions. In someembodiments, a compartment or a portion thereof (e.g., a wall portionforming the compartment within the applicator body 1205) may befractured by the application of sufficient force to the compartment. Insome embodiments, one or more first compositions may be disposed withinthe applicator body 1205 such that one or more second compositionsdisposed within the one or more ampoules 1210 and/or one or morecompartments may contact the one or more second compositions responsiveto the release of the one or more second compositions. A non-limitingexample of a first composition may include an alcohol (e.g., 2-propanol)or a gelling agent and a non-limiting example of a second compositionmay include a caustic formulation, such as a hydrogen peroxide solution.In some embodiments, the various compositions (e.g., the one or morefirst compositions and the one or more second compositions) may be mixedtogether before or concurrently with the application thereof.

In some embodiments, an applicator hub 1225 may be in fluidcommunication with the applicator body 1205 at a proximal end of theapplicator 1200. The applicator hub 1225 may be configured to receivethe compositions of embodiments herein that flow from the applicatorbody 1205 responsive to the release of the compositions of embodimentsherein from the ampoule 1210. In some embodiments, at least a portion ofthe applicator hub 1225 may be arranged within the applicator body 1205.In some embodiments, the applicator hub 1225 may be fixedly attached tothe applicator body 1205, such as through the use of adhesives, afriction fit, a press-fit, a threaded fit, or the like. In someembodiments, an outer portion of the applicator hub 1225 may be fixedlyattached to an inner portion of the proximal end of the applicator body1205. In some embodiments, the applicator hub 1225 may form a hermeticseal with the applicator body 1205 through a friction fit, adhesives, athreaded fit, or the like. In some embodiments, the applicator hub 1225may be formed from a polymer material, including, without limitation,PE, PP, HDPE, and LDPE. In some embodiments, a protective cap 1235 maybe configured to enclose the applicator hub 1225 at a proximal end ofthe applicator 1200.

In some embodiments, a filter 1220 may be arranged within the applicator1200 between the ampoule 1210 and the proximal end of the applicator1200. In some embodiments, the filter 1220 may be arranged within adistal portion of the applicator hub 1225 that faces the ampoule 1210.The filter 1220 may be configured to filter out pieces of the brokenampoule 1210 while allowing the compositions of embodiments herein toflow therethrough. The filter 1220 may be formed from various materials,including any material capable of filtering out the shards of theampoule from the compositions of embodiments herein. Non-limitingexamples of filter 1220 materials may include various polymer materials,PE, PP, HDPE, LDPE, polystyrene (PS), carbon, a foam material, ceramic,sand, diatomaceous earth (DE), paper fibers, and any combinationthereof. In some embodiments, the filter 1220 material may be selectedto provide a particular flow rate of the compositions of embodimentsherein through the filter.

In some embodiments, the applicator 1200 may include a tip 1230 arrangedat a proximal portion thereof. In some embodiments, the tip 1230 may befixedly arranged within a central bore of the applicator hub 1225. Thetip 1230 may be configured to facilitate the application of thecompositions of embodiments herein onto the skin of a patient. In someembodiments, the tip 1230 may be formed from an absorbent orsubstantially absorbent material. In some embodiments, the tip 1230 maybe configured as a sintered polymeric tip. In some embodiments, the tip1230 may be configured as a doe footed tip. In some embodiments, the tip1230 may be configured as a flocked tip, for example, that may includeand/or may be formed from a flocked material, including, withoutlimitation flock formed from filaments of various materials. In someembodiments, the flocked tip may be formed by affixing a flockedmaterial to the tip 1230. In some embodiments, the tip 1230 may beformed from various materials that are non-reactive or otherwisechemically compatible with the compositions of embodiments herein. Insome embodiments, the tip 1230 may be formed from various biocompatiblematerials. In some embodiments, the tip 1230 may be formed from variousmaterials, including, without limitation, cellulose, nylon, rayon,polyester, Teflon®, fibers thereof, flocked materials thereof, and anycombination thereof.

In some embodiments, the tip 1230 may be fixedly arranged within theapplicator 1200, such as in the applicator hub 1225, such as throughadhesives, a friction fit, a threaded fit, a snap or lock fit, apress-fit, or the like. In some embodiments, the applicator 1200 may beconfigured to allow replacement of the tip 1230 during or after eachuse. In some embodiments, the ampoule 1210 may be replaced within theapplicator 1200. For instance, an operator may remove the end cap 1215,remove the shards of a fractured ampoule 1210, and insert a new ampoulewith the same and/or different compositions of embodiments herein. Inthis manner, the applicator 1200 may be used multiple times and/or forthe treatment of multiple skin conditions (i.e., separate lesions,warts, or other skin formations) of the same patient. In someembodiments, the applicator 1200 may be a single use applicator. In someembodiments, the single use applicator is intended to be discarded aftera single use.

In some embodiments, the compositions of embodiments herein may bereleased from the ampoule 1210 and flow through the applicator body 1205(including any chambers thereof), the filter 1220, the applicator hub1225, and out of the applicator through the tip 1230. In someembodiments, the applicator body 1205 and/or the tip 1230 may beconfigured to allow an operator to control the flow of the causticformulation out of the applicator 1200. In a non-limiting example, afterthe compositions of embodiments herein have been released from theampoule 1210, an operator may initiate flow of the compositions ofembodiments herein out of the applicator 1200 by squeezing on theapplicator body 1205, thereby generating sufficient pressure therein toforce the compositions of embodiments herein to flow out through the tip1230. In some embodiments, pressing the tip 1230 on the skin of apatient may produce capillary action sufficient to cause thecompositions of embodiments herein that have been released from theampoule 1210 and are in contact with the tip to flow through the tip andout of the applicator 1200. In some embodiments, an operator may controlthe rate of the flow by varying a level of force used to squeeze thesides of the applicator body 1205 and/or press the tip 1230 against theskin of the patient. In some embodiments, the applicator 1200 mayinclude an actuator (not shown) configured to cause the compositions ofembodiments herein to be dispensed from the applicator.

In some embodiments, at least one portion of the applicator may includea hydrophobic material, such as the filter 1220 and/or the tip 1230. Insome embodiments the hydrophobic material is composed of polyester orco-polyester polymers, acrylic, modified acrylic (e.g., modacrylic),polypropylene, polyethylene or combinations or mixtures thereof. In someembodiments, for example, the filter may comprise a blend ofpolypropylene and polyester or co-polyester polymers. Non-limitingexamples of hydrophobic materials may also include materials including,coated with, and/or modified by silanes, alkylsilanes,fluoroalkylsilanes, silicone, combinations thereof, and derivativesthereof. In some embodiments, materials used to form the applicator andportions thereof according to some embodiments described herein may beimparted with hydrophobic properties by coating or otherwiseincorporating a hydrophobic material therein. In some embodiments, thehydrophobic portions of the applicator may operate to impede, reduce,prevent, and/or substantially prevent the compositions of embodimentsherein that have been released from the ampoule from flowing throughportions of the applicator and/or out of the tip of the applicator.

In some embodiments, the applicator 1200 may be configured such that thecompositions of embodiments herein released from the ampoule 1210 maynot be passively dispensed from the applicator 1200 without an operatorapplying pressure to the applicator, such as by squeezing or otherwiseapplying a force to the applicator body 1205. In some embodiments, therequirement for operator action (i.e., applying pressure to theapplicator 1200) may be facilitated by the use of hydrophobic materialsaccording to some embodiments. In some embodiments, the applicator 1200may be configured such that a void may be formed within the applicatorbody 1205 behind a volume of the compositions of embodiments hereinreleased from the ampoule 1210, for instance, when the applicator isorientated in a vertical, substantially vertical, or partially verticalposition. In some embodiments, the void may operate as a vacuum toimpede, reduce, restrict, prevent, and/or substantially prevent the flowof the compositions of embodiments herein released from the ampoule 1210out of the applicator 1200. In this manner, the hydrophobic portion ofthe applicator 1200 and/or a void formed within the applicator body 1205may operate to prevent the leakage of the compositions of embodimentsherein from the applicator after the compositions of embodiments hereinhave been released from the frangible ampoule 1210, including when theapplicator is in a position conducive to dispensing compositions ofembodiments herein, such as a vertical or substantially verticalposition.

The applicator 1200 may be configured to store, dispense, and apply anyof the compositions of embodiments herein as part of a method oftreatment for any of the conditions disclosed herein. For example, theapplicator 1200 may be configured to store, dispense, and apply atopical composition comprising 2-propanol and up to about 50% hydrogenperoxide. In some embodiments, the topical composition may be anycomposition described in embodiments herein.

FIGS. 13A-13C depict a first exploded side view, a second exploded sideview, and a cross-sectional view, respectively, of an illustrativeapplicator according to a second embodiment. As shown in FIGS. 13A-13C,an applicator 1300 may include an applicator body 1305 having an ampoule1310 arranged within an interior cavity thereof. A proximal end of theapplicator body 1305 may be enclosed by a protective cap 1325, forexample, when the applicator 1300 is not in use. A distal end of theapplicator body 1305 may be enclosed by an end cap 1315 fixedly attachedthereto, such as through adhesives, a friction fit, a snap or lockconnection, or the like. A holed flocked tip 1330 (may be arrangedwithin at least a portion of the applicator body 1305 at a proximal endthereof. In some embodiments, the holed flocked tip 1330 may be formedfrom or substantially from applicator hub 1225 and tip 1230 as depictedin FIG. 12. In some embodiments, the holed flocked tip 1330 may befixedly attached to the applicator body 1330, such as through adhesives,a friction fit, a threaded fit, a snap or lock fit, or the like. In someembodiments, a filter 1335 may be arranged within the holed flocked tip1330.

In some embodiments, a grip 1320 may be arranged on an exterior portionof the applicator body 1305 at a proximal end thereof. In someembodiments, the grip 1320 may be configured to improve the ability ofthe hand of an operator to hold and control the applicator 1300. In someembodiments, the grip 1320 may be formed from various polymer materials,including, without limitation, a foam material, a rubber material, aplastic material, a thermoplastic material, or other material known tothose having ordinary skill in the art, or any combination thereof. Insome embodiments, the grip 1320 may be configured to facilitate enhancedhand positioning, increased operator comfort, decreased hand fatigue, orthe like, when using the applicator 1300. In some embodiments, at leasta portion of the grip 1320 may include a contoured, curved, concave, orother non-flat surface configured to facilitate precise control of theapplicator 1300 by an operator. In some embodiments, the grip 1320 mayinclude at least one anti-roll feature configured to reduce or preventthe rolling or turning of the applicator 1300 in the hand of an operatorduring use thereof. In some embodiments, the grip 1320 may include atleast one anti-roll feature configured to reduce or prevent the rollingor turning of the applicator 1300 when placed on a surface, for example,a counter, a table, an instrument stand, or the like. In someembodiments, the grip 1320 may be over-molded onto the exterior surfaceof the applicator body 1305. In some embodiments, the grip 1320 may beconfigured as a separate element that may be slid on to, or otherwiseadjoined to or affixed to, the applicator 1300.

In some embodiments, a pressure area 1345 may be arranged on theapplicator body 1305. In some embodiments, the pressure area 1345 mayinclude a marked area configured to indicate to an operator an optimumarea on the applicator tube 1305 to apply pressure to fracture theampoule 1310. In some embodiments, the pressure area 1345 may beconfigured to receive the fingers and/or thumb of a user to facilitatethe grip of and/or the squeezing of the applicator tube 1305 to rupturethe ampoule 1310. In some embodiments, the pressure area 1345 mayinclude a marked area formed from one or more raised formations. In someembodiments, the pressure area 1345 may be formed from materials thatare molded onto an outside surface of the applicator body 1305. In someembodiments, the pressure area 1345 may include a printed and/or raisedfeature arranged on a label affixed to an outer surface of theapplicator body 1305. In some embodiments, the pressure area 1345 may beconfigured to concentrate pressure applied by an operator to rupture theampoule 1310. In some embodiments, the pressure area 1345 may beconfigured to indicate a position directly or substantially directlyabove one or more force concentration elements (not shown) locatedwithin the applicator body 1305 that are configured to concentratepressure applied by an operator to rupture the ampoule 1310. In someembodiments, the force concentration elements may include one or morestruts formed from various materials, such as a plastic material. Insome embodiments, the force concentration elements are not present inthe applicator 1300. In some embodiments, finger pressure is sufficientto rupture the ampoule 1310. In some embodiments, the pressure area 1345may be formed from a more flexible material than the other portions ofthe applicator tube 1305 to facilitate the transfer of pressure from thehand of an operator squeezing on the applicator tube 1305 to the ampoule1310. In an embodiment in which the applicator 1300 includes a pluralityof ampoules 1310 and/or one or more compartments (not shown), theapplicator may include a plurality of pressure areas 1345 configured toindicate an optimum area to apply pressure to fracture each compartmentand/or ampoule.

In some embodiments, the ampoule 1310 may be fixedly arranged within theapplicator body 1305. For example, in some embodiments, the ampoule maybe fixedly arranged within the applicator body 1305 such that theampoule does not does not move or substantially does not movelongitudinally within the applicator body 1305 or does not moveproximally beyond a certain position within the applicator body. In someembodiments, the size and/or shape of the ampoule 1310 may be configuredto correspond with the size and/or shape of the applicator body 1305(for instance, an inner dimension of the applicator body) such that theapplicator body holds the ampoule in place therein through a frictionfit. In some embodiments, the applicator body 1305 may include a varyinginner dimension such that the ampoule 1310 may only fit within a certainportion of the applicator body. In some embodiments, the inner surfaceof the applicator body 1305 may include bumps, ridges, projections, orother structures configured to hold the ampoule 1310 in place and/or toprevent the ampoule from moving longitudinally within the applicatorbody. In some embodiments, a support structure 1340 may be arrangedwithin the applicator body to hold the ampoule 1310 in place and/or toprevent the ampoule from moving longitudinally within the applicatorbody 1305. In some embodiments, the support structure 1340 may includeone or more struts or projections (e.g., ridges, bumps, or the like)arranged within and/or formed from portions of the applicator body 1305.In some embodiments, the support structure 1340 may be configured toposition the ampoule for breakage by an operator. For example, thesupport structure 1340 may be configured to maintain the within an areacorresponding with the pressure area 1345.

In some embodiments, the applicator 1300 may include one or moredebriding elements (not shown) arranged on an exterior portion of theapplicator, such as the applicator body 1305, the end cap 1315, and/orthe protective cap 1325. The one or more debriding elements may beconfigured to mechanically or physically abrade, ablate, thin, curette,destruct, remove, excise, or otherwise debride an area of skin of apatient, such as an area of skin having a lesion, wart, seborrheickeratosis, or other skin formation. In some embodiments, the one or moredebriding elements may be configured to disturb the surface of, decreasethe size of, decrease the thickness of, and/or decrease the volume of alesion or other skin formation. In some embodiments, the one or moredebriding elements may include an abrasive element, a sharp, a tip, acurette, or any other element and/or formation capable of debriding orotherwise effecting a lesion or other skin formation. In suchembodiments, an operator may use the one or more debriding elements todebride or otherwise effect a lesion or other skin formation before,after, and/or during application of the compositions of embodimentsherein via the applicator 1300.

FIGS. 14A and 14B depict multiple views of the applicator body accordingto some embodiments. As shown in the side view A of FIG. 14A, theapplicator body 1400 may include a housing 1405 having a pressure area1445 arranged thereon. As depicted in internal view B of FIG. 14A, theapplicator body 1400 may include a support structure 1440 arrangedtherein. An end cap 1415 may be configured to be coupled, includingremovably coupled, to a distal end 1420 of the applicator body 1400.FIG. 14B depicts a side view A and a top-down view B of an applicatorbody having a grip 1425.

FIG. 15 depicts an illustrative end cap of an applicator according tosome embodiments. In particular, FIG. 15 depicts a side view A, atop-down view B, and an internal side view C of an end cap 1500. FIG. 16depicts a holed flocked tip (or “applicator hub”) according to someembodiments. More specifically, FIG. 16 depicts an internal side view A,a side view B, and a top-down view C of a holed flocked tip 1600. Asshown in side view B of FIG. 16, the holed flocked tip 1600 may includea flocked portion 1605 and an injection gate portion 1610.

FIG. 17A depicts an internal side view of a protective cap 1700according to some embodiments, including detail 1705 for the distalportion 1710 of the protective cap. FIG. 17B depicts the protective cap1700 arranged on a portion of the applicator body 1710 and enclosing atip 1720 of the applicator according to some embodiments. FIGS. 18A and18B depict a side view and an internal view, respectively, of anapplicator 1800 according to some embodiments. As shown in FIG. 18A, theapplicator 1800 may include an applicator body 1805 enclosed by aprotective cap 1810. FIG. 18B depicts an internal view of a protectivecap 1810 having a spine 1815 extending from an internal surface thereof.When the protective cap 1810 is coupled to the applicator body 1805, thespine 1815 may engage or interface with the holed flocked tip 1820. Insome embodiments, the spine 1815 may plug, block, or otherwise close oneor more holes in the holed flocked tip 1820, preventing, for instance,fluid from exiting the holed flocked tip. While embodiments set forthherein are described in terms of “comprising”, all of the foregoingembodiments also include compositions and methods that consist of onlythe ingredients or steps recited or consist essentially of theingredients and steps recited, and optionally additional ingredients orsteps that do not materially affect the basic and novel properties ofthe composition or method.

This disclosure and embodiments illustrating the method and materialsused may be further understood by reference to the followingnon-limiting examples.

Example 1

A seborrheic keratosis (SK) lesion on a 76 year old female withFitzpatrick skin type 1 was treated with a solution comprised of 40%stabilized hydrogen peroxide and 5% 2-propanol. After cleansing the skinwith 70% 2-propanol, the hydrogen peroxide solution was appliedtopically to the seborrheic keratosis lesion using a flocked doe-footshaped applicator. Using firm pressure and an application technique thatwas appropriate for the target lesion size, the solution was applied forapproximately 20-30 seconds. After approximately 1-2 minutes, theapplication process was repeated. This sequence was repeated until 4applications had been performed. There was no pain or discomfort duringthe procedure. Follow-up one week later revealed the SK lesion to beresolving. Follow-up 3 weeks after treatment revealed the lesion to beresolving, but not completely cleared. A second treatment sessionidentical to the first was performed 3 weeks after the first treatment.Follow-up 5 weeks and 8 weeks after the second treatment revealed thelesion was completely resolved with no evidence of recurrence of thelesion and no adverse cosmetic sequalae (e.g., scarring or pigmentarychange (hyperpigmentation or hypopigmentation)). The subject wasextremely pleased with the results.

Example 2

A seborrheic keratosis (SK) lesion on a 65 year old female withFitzpatrick skin type 4 was treated with a solution comprised of 32.5%stabilized hydrogen peroxide and 5% 2-propanol. After cleansing of theskin with 70% 2-propanol, the solution was applied topically to theseborrheic keratosis lesion using a flocked doe-foot shaped applicator.Using firm pressure and an application technique that was appropriatefor the target lesion size, the solution was applied for approximately20-30 seconds. After approximately 1-2 minutes, the application processwas repeated. This sequence was repeated until 4 applications had beenperformed. There was no pain or discomfort during the procedure.Follow-up 3 weeks after treatment revealed the lesion to completelyresolved with no evidence of scarring or pigmentary change(hyperpigmentation or hypopigmentation). The subject was extremelypleased with the results. Follow-up 11 weeks after the treatmentrevealed no recurrence of the lesion and no adverse cosmetic sequalae.

Example 3

A seborrheic keratosis (SK) lesion on a 73 year old male withFitzpatrick skin type 3 was treated with a solution comprised of 25%stabilized hydrogen peroxide and 5% 2-propanol. After cleansing of theskin with 70% 2-propanol, the solution was applied topically to theseborrheic keratosis lesion using a flocked doe-foot shaped applicator.Using firm pressure and an application technique that was appropriatefor the target lesion size, the solution was applied for approximately20-30 seconds. After approximately 1-2 minutes, the application processwas repeated. This sequence was repeated until 4 applications had beenperformed. There was no pain or discomfort during the procedure.Follow-up 3 weeks after treatment revealed the lesion to be improved,but not completely resolved. A second treatment session identical to thefirst was performed 3 weeks after the first treatment. Follow-up 1 weekafter the second treatment session revealed the SK lesion to becompletely resolved with no evidence of scarring or pigmentary change(hyperpigmentation or hypopigmentation). Follow-up 8 weeks after thesecond treatment (11 weeks after the first treatment) revealed norecurrence of the lesion and no adverse cosmetic sequalae. The subjectwas extremely pleased with the results.

Example 4

A common wart (verruca) on the cheek of a 56 year old white male(Fitzpatrick Type 2 skin) was treated with a solution comprising 40%hydrogen peroxide (FMC/PeroxiChem “Super D”), and 5% 2-propanol(Spectrum Chemical USP Grade). After cleansing of the skin with 70%2-propanol, the solution was applied topically to the seborrheickeratosis lesion using a flocked doe-foot shaped applicator. Using firmpressure and an application technique that was appropriate for thetarget lesion size, the solution was applied for approximately 20-30seconds. After approximately 1-2 minutes, the application process wasrepeated. This sequence was repeated until 4 applications had beenperformed. There was no pain or discomfort during the procedure. Overthe next several days the lesion evidenced superficial crusting and milderythema (redness). Follow-up 2 weeks after the treatment revealed theverruca to be completely resolved with no erythema and no evidence ofscarring or pigmentary change (hyperpigmentation or hypopigmentation).Follow-up 8 weeks after the treatment revealed no recurrence of thelesion and no adverse cosmetic sequalae. The subject was extremelypleased with the results.

Example 5

A randomized, double-blind, vehicle-controlled, parallel group study wasconducted with 22 subjects, to evaluate the effectiveness of a 40%topical solution of hydrogen peroxide and 5% 2-propanol when appliedonce weekly (with a maximum of 4 applications) to treatment-naïve commonwarts on the extremities (not periungual or subungual) compared with amatching topical solution vehicle. The treatment protocol included (1)cleansing the target wart by rubbing with a swab/wipe wetted with 70%2-propanol; (2) wetting the supplied applicator with a quantity of studymedication sufficient to wet the target wart with a thin film; (3)applying the study medication to the target wart for approximately 10seconds using firm pressure and a circular motion; (4) absorbing excessstudy medication with a clean absorbent wipe (or equivalent) to minimizeexposure to normal surrounding skin; (5) repeating the applicationprocedure 3 times after a waiting period of about 20 seconds after eachapplication. After completing the third study medication application tothe target wart, the target wart was not disturbed until all visiblereaction, if any, had stopped. After approximately 10 minutes, anyremaining study medication was absorbed and the target wart was driedwithout wiping or rubbing. 17 subjects completed all four weeklytreatments. All subjects tolerated the procedure well, no adverse eventswere reported, and local skin reactions were reported as none or mild.While no wart lesions were completely resolved at the conclusion of thispilot study (4 weekly doses)—it was expected that some of the wartlesions would show improvement, but that complete cure of the lesionsmight take more than four treatments (e.g., up to 10 or up to 30treatments or more)—which is common with topical wart treatments—(e.g.,over-the-counter daily salicylic acid treatments) or would require morefrequent application than weekly (e.g., twice weekly or daily)—astatistically significant improvement in the lesions was demonstratedand the proof-of concept was validated. Subjects showed a statisticallysignificant improvement in wart severity as measured by the mean WartImprovement Assessment score by visit (FIG. 8) and by the mean change inbaseline in the Wart Severity Assessment score by visit (FIG. 9). FIG. 7describes the Wart Improvement Assessment score and Wart SeverityAssessment score.

Example 6

In vitro Drug Release and in vitro Skin Permeation studies wereperformed. Thirteen formulations of 40% w/w hydrogen peroxide wereprepared using a stock solution of 50% FMC/PeroxyChem “Super D”stabilized hydrogen peroxide as the peroxide source, with differentlevels of 1 and 2-propanol for assessment—as indicated in Table 1.

TABLE 1 Formulation and composition of excipients (% w/w) ExcipientP1-20 P1-15 P1-10 P1-5 P1-2.5 P1-1 P2-20 P2-15 P2-10 P-2-5 P2-2.5 P2-1Control H2O2 (50% w/w) 80.00 80.00 80.00 80.00 80.00 80.00 80.00 80.0080.00 80.00 80.00 80.00 80.00 1-propanol 20.00 15.00 10.00  5.00  2.50 1.00 — — — — — — — 2-propanol — — — — — — 20.00 15.00 10.00  5.00  2.50 1.00 — Triethanolamine To pH 3.5 Deionized water — q.s. 100% — q.s.100%

An in vitro drug release study (based on SUPAC guidelines) with the 13formulations was performed. The receiver fluid was PBS, the syntheticmembrane was silicone (selected after preliminary suitability studies),and sampling volume was 1 mL with 1 mL replenished. The measurement timepoints were at 0 min, 0.5 hr, 1 hr, 2 hr, 4 hr, 6 hr, and 8 hr. FIG. 1illustrates the mean cumulative amount of hydrogen peroxide released perunit area following application of all formulations. FIGS. 2 and 3compare the release of hydrogen peroxide between formulations containing1- and 2-propanol, respectively, demonstrating that, in general,increasing either 1-propanol or 2-propanol content in the formulationsproduces an increase in the amount of hydrogen peroxide released acrossthe silicone membrane.

While in general, a higher amount of hydrogen peroxide is releasedfollowing application of formulations containing 1-propanol compared to2-propanol on a w/w basis, this trend is most apparent in the 1-propanolformulations and in formulations of higher concentrations of thealcohols—beginning at approximately above 5% alcohol concentration—andobserved to a much greater degree as the alcohol concentration increasesto 10%, 15% and 20%. This effect is illustrated by FIG. 4, which showsthe steady state release of hydrogen peroxide between 0.5 h and 4 h forthe different concentrations of 1-propanol and 2-propanol and FIG. 5,which shows the difference in steady state release of hydrogen peroxidebetween formulations containing 1-propanol and 2-propanol at levels of5-20% w/w. For formulations containing 1-propanol, there is an increasein the steady state release of hydrogen peroxide (over 0.5 to 4 h) onincreasing 1-propanol content, however for formulations containing2-propanol, the steady state release of hydrogen peroxide appears toremain essentially constant across the tested concentrations of2-propanol.

Surprisingly, and importantly, this effect of the rate of release (0.5-4h) of hydrogen peroxide from 1-propanol formulations being greater thancorresponding 2-propanol formulations is reversed at lowerconcentrations of the alcohols, e.g., below approximately 5% alcohol,with the rate of hydrogen peroxide release from the 2-propanolformulations at lower alcohol concentrations (e.g., <5%) being greaterthan the rate of hydrogen peroxide release from the 1-propanolcontaining formulations. Therefore, in the lower range of alcoholconcentrations to be incorporated in a preferred embodiment of theformulation, which is most desirable, as minimizing the concentration ofthe alcohol to be added may minimize the potential impurities introducedinto the peroxide formulation, it is unexpectedly discovered that2-propanol may be preferred over 1-propanol. Without wishing to be boundby theory, it appears that the rate of release of hydrogen peroxide atlower concentrations of 2-propanol will greater than for the 1-propanol.

Example 7

Oxidation assessment by redox potential measurement: Assessment ofoxidation (by measuring redox potential) was performed on 13 prepared40% w/w hydrogen peroxide formulations as summarized in Table 1 with andwithout skin at t=0, 1, 6 and 24 hr (n=3 repetitions was performed). Theredox potential data of each of the 13 formulations summarized in Table1 above is illustrated in FIG. 10.

While for formulations containing less than 5% w/w propanol, the datawere not statistically significant, for formulations containing 5% to20% w/w propanol, a higher (more positive) redox potential was measuredfor formulations containing 1-propanol when compared to 2-propanol. Thatis, 1-propanol, when incorporated into hydrogen peroxide formulations inthis concentration range (i.e. 40%), will have a greater propensity tobe oxidized than 2-propanol when incorporated into these same hydrogenperoxide formulations. A similar trend is observed in the presence ofskin, where the relative redox potential between the 1-propanol and2-propanol containing formulations is maintained. The data for the studyinvestigating the redox potential of 40% w/w hydrogen peroxideformulations containing 5% w/w 1- or 2-propanol, both with and withoutskin is illustrated in FIG. 11. Thus, while it may be theoreticallyexpected that secondary alcohols, (e.g., 2-propanol) are inherently lessstable in high concentrations of hydrogen peroxide than primaryalcohols, this unexpected result, in fact, demonstrates that 2-propanolis less likely to be oxidized than 1-propanol in these embodiments, andit would be preferable to incorporate 2-propanol into these solutions.

Example 8

Surface tension analysis was performed on the 13 40% hydrogen peroxideformulations with varying 1-propanol or 2-propanol concentrations fromTable 1 at 37° C. (in duplicate) using Kruss Tensiometer and theWilhelmy Plate technique. Calibration of the system using deionisedwater showed results within 1.0 mN/m of the literature values at 37° C.(ca. 70 mN/m). Each sample had a 30 minute run time and the result wascalculated from the mean of the last 10 readings.

Analysis of the samples was performed in duplicate at 37±0.5° C. using aconfidence level of ±1.4%. Where the obtained duplicate results wereoutside this range, a third test was performed and the reported resultwas calculated using the 2 closest individual results. All data has beenpresented in Table 2 below and illustrated in FIG. 6.

TABLE 2 Surface Tension (mN/m) Range Formulation Results (1st and lastreading) Rounded mean P1-20 29.65 28.05-29.76 29.8 ± 0.4 29.8628.03-29.88 P1-15 33.44 29.61-33.76 33.3 ± 0.5 33.22 29.71-33.91 P1-1035.42 32.84-35.30 32.9 ± 0.5 33.03 32.79-32.96 (Tests 2 and 3) 32.8032.64-32.84 P1-5 38.90 39.99-38.62 38.7 ± 0.5 38.46 38.79-38.45 P1-2.545.95 45.56-45.95 45.7 ± 0.6 45.34 46.16-45.33 P1-1 51.58 52.37-51.4651.0 ± 0.7 50.35 51.76-50.24 P2-20 32.76 33.89-32.59 32.6 ± 0.5 32.3534.03-32.20 P2-15 34.28 36.99-34.10 35.9 ± 0.5 35.76 36.99-35.59 (Tests2 and 3) 36.11 36.94-35.96 P2-10 41.14 41.16-41.23 41.1 ± 0.6 41.1340.77-41.26 P2-5 47.73 48.36-47.75 48.3 ± 0.7 48.95 48.61-49.12 P2-2.553.54 54.42-53.46 54.1 ± 0.8 54.66 54.88-54.66 P2-1 59.85 62.01-59.5960.2 ± 0.8 61.87 62.38-61.67 (Tests 1 and 3) 60.59 62.25-60.35 Control58.92 61.30-58.66 60.3 ± 0.8 60.63 65.30-60.18 (Tests 2 and 3) 59.9965.33-59.49

The data demonstrate that, in general, incorporating either 1-propanolor 2-propanol decreases the surface tension of the tested hydrogenperoxide formulations, and that this surface-tension decreasing effectis roughly proportional to the concentration of the added 1-propanol or2-propanol. Theoretically, from a surface-tension point of view, eithermight be thought to be useful to incorporate into the embodimentsdisclosed herein.

However, the effect of the surface-tension reduction of 1-propanol onthe peroxide formulations is more potent than that of 2-propanol suchthat in the preferred embodiments formulations containing 1-propanolwill have a much lower surface tension than the corresponding 2-propanolformulations, and will be much more likely to spread out of the area ofapplication and off the lesion, on to surrounding non-lesional skinthereby lowering the effectiveness of the therapeutic and serving as asubstrate for ADH in the skin—resulting in increased irritation,erythema, and adverse cutaneous effects irritating the surrounding skin.40% hydrogen peroxide was employed in this illustrative study andexamples, but by varying the concentration of the alcohol (e.g.,2-propanol) component in other hydrogen peroxide compositions of theembodiments described herein (e.g., in concentrations of hydrogenperoxide of 25%, 32.5%, 40%, 42.5%), an optimal concentration of thealcohol that will produce the optimal surface tension reduction, achievethe desired clinical effect, and minimize the risk of local adversecutaneous effects may be readily determined.

Example 9

Solutions were prepared using stabilized hydrogen peroxide (Peroxal CG50® Arkema, Inc.) and 2-propanol 99% (Spectrum Chemical, USP Grade) tomake a composition comprising 40% stabilized hydrogen peroxide and 5%2-propanol and a composition comprising 25% stabilized hydrogen peroxideand 5% 2-propanol. The solutions were placed on stability in Type Iamber borosilicate glass screw-top vials and maintained at 25° C./60%relative humidity (RH); 40° C./75% RH; and 5° C. (refrigerated). The 25%stabilized H₂O₂/5% IPA solutions remained stable (“in specification”according to ICH Harmonised Tripartite Guideline: Stability Testing ofNew Drug Substances and Products Q1A(R2)”, current Step 4 version, dated6 Feb. 2003) under the 40° C. conditions at 6 months, and under both the25° C. conditions and 5° C. conditions at 24 months. The 40% stabilizedH₂O₂/5% IPA solutions remained stable (“in specification” according toICH Harmonised Tripartite Guideline: Stability Testing of New DrugSubstances and Products Q1A(R2)”, current Step 4 version, dated 6 Feb.2003) under the 40° C. conditions at 6 months, under both the 25° C.conditions and 5° C. conditions at 24 months.

Example 10

Solutions were prepared using stabilized hydrogen peroxide (Peroxal CG50® Arkema, Inc.) and 2-propanol 99% (Spectrum Chemical, USP Grade) tomake a composition comprising 40% stabilized hydrogen peroxide and 15%2-propanol and a composition comprising 25% stabilized hydrogen peroxideand 15% 2-propanol. The solutions were placed on stability in Type Iamber borosilicate glass screw-top vials and maintained at 25° C./60%relative humidity (RH); 40° C./75% RH; and 5° C. (refrigerated). The 25%stabilized H₂O₂/15% IPA solutions remained stable (“in specification”according to ICH Harmonised Tripartite Guideline: Stability Testing ofNew Drug Substances and Products Q1A(R2)”, current Step 4 version, dated6 Feb. 2003) under the 40° C. conditions at 6 months, and under both the5° C. and 25° C. conditions at 24 months. The 40% stabilized H₂O₂/15%IPA solutions remained stable (“in specification” according to ICHHarmonised Tripartite Guideline: Stability Testing of New DrugSubstances and Products Q1A(R2)”, current Step 4 version, dated 6 Feb.2003) under the 40° C. conditions at 6 months, and under both the 5° C.and 25° C. conditions at 24 months.

Example 11

Solutions were prepared using stabilized hydrogen peroxide(FMC/PeroxyChem “Super D 50%” (FMC/PeroxyChem) and 2-propanol 99%(Spectrum Chemical, USP Grade) to make a composition comprising 45%stabilized hydrogen peroxide and 5% 2-propanol. The solutions wereplaced on stability in Type 1 amber borosilicate glass vials instability chambers and maintained at 25° C./60% relative humidity (RH),40° C./75% RH, and 5° C. (refrigerated). The 45% stabilized H₂O₂/5% IPAsolutions remained stable (“in specification” according to ICHHarmonised Tripartite Guideline: Stability Testing of New DrugSubstances and Products Q1A(R2)”, current Step 4 version, dated 6 Feb.2003) under the under the 40° C. conditions at 6 months, and under boththe 5° C. and 25° C. conditions at 12 months.

Example 12

Solutions were prepared using stabilized hydrogen peroxide(FMC/PeroxyChem “Super D 50%” (FMC/PeroxyChem) and 2-propanol 99%(Spectrum Chemical, USP Grade) to make a composition comprising 40%stabilized hydrogen peroxide and 5% 2-propanol. The solutions werealiquoted into heat-sealed crushable glass ampules. Thesolutions/ampules were placed on stability in chambers and maintained at25° C./60% relative humidity (RH); 40° C./75% RH; and 5° C.(refrigerated) conditions. The 40% stabilized H₂O₂/5% IPA solutionsremain stable (“in specification” according to ICH Harmonised TripartiteGuideline: Stability Testing of New Drug Substances and ProductsQ1A(R2)”, current Step 4 version, dated 6 Feb. 2003) under both the 5°C. and 25° C. conditions at 12 months thus far.

Example 13

Solutions were prepared using stabilized hydrogen peroxide(FMC/PeroxyChem “Super D 50%” (FMC/PeroxyChem, Inc.) and 2-propanol 99%(Spectrum Chemical, USP Grade) to make a composition comprising 40%stabilized hydrogen peroxide and 5% 2-propanol. The solutions wereprepared and aliquoted into amber, Type I borosilicate glass screw-topvials. Solutions were placed on stability in chambers and maintained at25° C./60% relative humidity (RH) and 5° C. (refrigerated) conditions.The 40% stabilized H₂O₂/5% IPA solutions remain stable (“inspecification” according to ICH Harmonised Tripartite Guideline:Stability Testing of New Drug Substances and Products Q1A(R2)”, currentStep 4 version, dated 6 Feb. 2003) under both the 25° C. conditions and5° C. conditions at 12 months thus far.

Example 14

The following formulations were prepared using stabilized hydrogenperoxide (Peroxal CG 50® Arkema, Inc.), 2-propanol 99% (SpectrumChemical, USP Grade) comprising about 44% to about 46% (w/w) stabilizedhydrogen peroxide, 0% or 5% 2-propanol (as indicated in TABLE 3) and agelling agent comprising either Carbopol ETD 2020, Carbopol 974P, orCarbopol Ultrez 10, in a concentration as indicated in TABLE 3. DisodiumEDTA was also incorporated into all formulations as a chelating agent,and pH was adjusted to between about pH 3.5-about pH 4.0. In order tomaximize the level of hydrogen peroxide in the gel formulations, the pHadjustment step (using 1% and 10% triethylamine) was performed after theformulations were prepared and therefore the composition (%weight-for-weight) in Table 3 is represented as the actual concentrationof the formulations placed on stability.

TABLE 3 Gel Formulations Hydrogen Peroxide Gelling Agent 2-propanol45.91% 0.48% w/w Carbopol ETD 0% 2020 46.11% 0.48% w/w Carbopol 974 P 0%45.23% 0.47% w/w Carbopol Ultrez 10 0% 44.29% 0.49% w/w Carbopol 974 P5%

The formulations were placed on stability in chambers and maintained at25° C./60% relative humidity (RH); 40° C./75% RH; and 5° C.(refrigerated). The stabilized hydrogen peroxide gel formulations abovewere assessed for stability and based on evaluation of hydrogen peroxiderecovery, pH, and Brookfield viscosity indicated that after t=6 weeksthe Carbopol ETD, Carbopol 974 P, and Carbopol Ultrez 10 2020 maintainedtheir hydrogen peroxide concentrations and their chemical & physicalstability. Stability of this length of time is sufficient stability fora two-part gel formulation (or three or more part formulation withadditional excipients such as IPA) mixed at or immediately before thetime of application where, e.g., the hydrogen peroxide and the gellingagent are kept in separate compartments (e.g., separated by a frangible,in separate vials, separate syringes) and combined or mixed when needed.

Example 15

A randomized, double-blind, vehicle-controlled, within-subjectcomparison study of the safety, tolerability and effectiveness ofhydrogen peroxide/2-propanol solutions in subjects with seborrheickeratosis was conducted. The main objective of this study was toevaluate the effectiveness of three different hydrogen peroxide/5%2-propanol solutions (25% H₂O₂, 32.5% H₂O₂, and 40% H₂O₂) when appliedto seborrheic keratosis (SK) target lesions on the back compared with amatching Vehicle. Secondary objectives included evaluating the safetyand tolerability of the active solutions when applied topically insubjects with SK. Thirty-two subjects completed the study and wereincluded in efficacy analyses. Subjects all had stable, clinicallytypical SKs, with at appropriate SK target lesions on the back.

Subjects were randomized to study medication (a unique study medicationfor each target lesion) and the study medications were applied to theassigned target lesions, each target lesion treated with a differentstudy medication at Day 1. At follow-up 3 weeks after initial medicationapplication, any target lesion that was not completely resolved receiveda retreatment study medication application. Subjects were followed up toevaluate treatment effects for a total of 78 days after the second studymedication application.

A statistically significant difference in the efficacy of the activeversus vehicle was first seen with the 40% solution beginning at Day 29,seven days after the second treatment. The length of the longest axis,the length of the perpendicular axis, and the height of the targetlesion all showed statistically significant improvement compared withvehicle. All concentrations of the formulation were generally welltolerated, with only a mild “stinging” at the time of solutionapplication and with mild dose-related transient local skin reactions(e.g., edema, erythema) at the time of application of the solution.There were no long-term pigmentary changes observed.

Example 16

A randomized, double-blind, vehicle-controlled, parallel group study wasconducted using formulations of (i) 40% w/w hydrogen peroxide and 5%2-propanol, (ii) 32.5% w/w hydrogen peroxide and 5% 2-propanol, and(iii) a vehicle solution for the treatment of seborrheic keratosislesions on the trunk and extremities of patients. The main objective ofthis study was to evaluate the dose-response relationship of 2concentrations of the hydrogen peroxide composition and its matchingvehicle when applied to SK target lesions on the trunk/extremities. Afurther objective was to evaluate the safety and efficacy of 2concentrations of the hydrogen peroxide composition and its matchingvehicle when applied topically up to 2 times to SK target lesions on thetrunk/extremities. The investigators identified four eligible SK targetlesions on each subject. Each target lesion was treated a maximum of twotimes. For each subject, the four target lesions were all on thetrunk/extremities. The skin of the patient was first cleansed with 70%2-propanol, and a thin film of the hydrogen peroxide formulation wasapplied topically to the seborrheic keratosis lesion(s) on thetrunk/extremities using a flocked doe-foot shaped applicator. Using firmpressure and an application technique that was appropriate for thetarget lesion size (e.g., dab and roll the applicator on smallerlesions; rub using a circular motion on larger lesions), the solutionwas applied for approximately 20-30 seconds. The investigator took careto minimize exposure to the surrounding normal skin. During theapplication process, excess study medication was removed from thesurrounding skin using a clean absorbent wipe. The investigator ensuredthe target lesion was wet with study medication at the end of the 20-30seconds and allowed the target lesion to remain undisturbed forapproximately 1-2 minutes. This sequence was repeated up to 4 times witha break of 1-2 minutes in between applications. Follow-up was performedat numerous time points including 1 and 3 weeks after treatment. Ifneeded, a second treatment session identical to the first was performed3 weeks after the first treatment. Lesions were evaluated to assesstheir clinical response 12 weeks after the final treatment. One hundredsixty-nine subjects completed the study. The primary endpoint, the meanof per-subject percentages of target lesions judged to be clear on thePLA (Physician's Lesion Assessment) scale at the last visit was 45.1%for the 40% w/w hydrogen peroxide and 5% 2-propanol, and 26.8% for the32.5% w/w hydrogen peroxide and 5% 2-propanol, compared with 4.8% forvehicle. A significantly greater improvement with both formulationscompared with vehicle was seen starting at the first evaluation, with adose response apparent at each visit. Local skin reactions werepredominantly mild. The results of this study confirmed that the topicalapplication of both the 40% H₂O₂ and 32.5% H₂O₂ solutions to SK lesionsusing the prescribed method, and formulations has the potential tosafely and effectively resolve SK lesions without the need for analgesiaand/or anesthesia, and with a minimal risk of hypopigmentation,hyperpigmentation, or scarring.

Example 17

A randomized, double-blind, vehicle-controlled, parallel group study wasconducted using formulations of (i) 40% w/w hydrogen peroxide and 5%2-propanol, (ii) 32.5% w/w hydrogen peroxide and 5% 2-propanol, and(iii) a solution vehicle for the treatment of seborrheic keratosislesions on the face of patients. The main objective of this study was toevaluate the dose-response relationship of two concentrations of thehydrogen peroxide composition and its matching vehicle when applied toSK target lesions on the face. A further objective was to evaluate thesafety and efficacy of two concentrations of the hydrogen peroxidecomposition and its matching vehicle when applied topically up to twotimes to SK target lesions on the face. The investigator identified oneeligible SK target lesions on each subject's face. The target lesion wastreated a maximum of two times. An oil based protectant (such as 100%white petrolatum) was optionally applied along the orbital rim and atthe medial and lateral canthi; gently stretch the periorbital skinbetween the thumb and forefinger at the time of petrolatum applicationto distend any periorbital rhytides (e.g., “crow's feet”) and ensurefull coverage of the skin at the base of the rhytides to decrease thelikelihood of tracking of the study medication towards the eye. Thesubject was additionally instructed to hold an absorbent pad in theappropriate area of the eye to absorb any excess study medication thatmight track away from the target lesion and to keep both eyes closedduring the entire study medication application procedure. The skin ofthe patient was first cleansed with 70% 2-propanol, and a thin film ofthe hydrogen peroxide formulation was applied topically to theseborrheic keratosis lesion(s) on the patient's face using a flockeddoe-foot shaped applicator. Using firm pressure and an applicationtechnique that was appropriate for the target lesion size (e.g., dab androll the applicator on smaller lesions; rub using a circular motion onlarger lesions), the solution was applied for approximately 20-30seconds. The investigator took care to minimize exposure to thesurrounding normal skin. During the application process, excess studymedication was removed from the surrounding skin using a clean absorbentwipe. The investigator ensured the target lesion was wet with studymedication at the end of the 20-30 seconds and allowed the target lesionto remain undisturbed for approximately 60 seconds. This sequence wasrepeated up to 4 times with a break of 1-2 minutes in betweenapplications. Follow-up was at several time points including 3 weeksafter treatment. If needed, a second treatment session identical to thefirst was performed 3 weeks after the first treatment. Lesions wereevaluated to assess their clinical response 12 weeks after the finaltreatment. One hundred sixteen subjects completed the study. The primaryendpoint was a pairwise comparison between the vehicle and each activemedication group based on mean change from baseline in PLA (Physician'sLesion Assessment) score at each post-baseline visit using ANCOVA. Asignificantly greater improvement with both formulations compared withvehicle was seen starting at the first evaluation, with a dose responseapparent at each visit. Local skin reactions were predominantly mild.The results of this study confirmed that the topical application of boththe 40% H₂O₂ and 32.5% H₂O₂ solutions to SK lesions on the face usingthe prescribed method and formulations has the potential to safely andeffectively resolve SK lesions without the need for analgesia and/oranesthesia, and with a minimal risk of hypopigmentation,hyperpigmentation, or scarring.

Example 18

A 60 year old white male with Fitzpatrick Type III skin had applicationsof a topical solution comprising 40% H2O2 and 5% IPA to a clinicallytypical appearing ovoid seborrheic keratosis in the right temporal areameasuring 18.7×24.0 mm in size. Prior to commencing the application ofthe solution, petroleum jelly was applied with a cotton-tippedapplicator to the area surrounding the keratotic lesion in order toprevent the solution from tracking along static and dynamic rhytides andbetter confine the solution to the lesion.

The solution was applied as described: The target lesion was thoroughlycleansed by firmly rubbing with a cotton-tipped applicator wetted with70% isopropyl alcohol (IPA). Care was taken to keep the IPA and the H2O2solution vial away from the face of the subject. After cleansing thelesion, the applicator, a nylon flocked doe-foot shaped applicator waswetted with a quantity of peroxide/IPA solution study medicationsufficient to wet the target lesion with a thin film. Usingmedium-to-firm pressure and an application technique that wasappropriate for the target lesion size, the solution was applied using acircular motion in an amount sufficient to cover the entire surface ofthe lesion (seborrheic keratosis) for approximately 30 seconds. Care wastaken to minimize exposure to the surrounding normal skin. During theapplication process excess study medication was removed from thesurrounding skin using a clean absorbent wipe to dab away any excess.The target lesion was then allowed to remain undisturbed forapproximately 1-2 minutes. The solution remained confined to the area ofapplication on the skin lesion. After the approximately 1-2 minutes, theapplication process was repeated until the peroxide/IPA solution hadbeen applied to the target lesion a total of 4 times.

The procedure was well tolerated and without complications. The maximaldiscomfort was described as a “stinging” that peaked at “about 1” (mild)on a 5-point scale (0-4). At the conclusion of the application session,the area demonstrated a “superficial whitening” reaction that extendedover only the area of application of the solution, with minimalaccompanying erythema. No solution ran-off the lesion and there was nowhitening or any adverse effect outside the area of application. Uponquestioning approximately 20 minutes following the last application, thediscomfort was noted to have already completely resolved (was rated at“0/4). Evaluation about 75 minutes after the last application revealedalmost complete resolution of the “superficial whitening” reaction.

Over the next several days, superficial crusting developed over thetreated area and over the next several weeks the lesion sloughed offwithout complication. Follow-up 38 days after the initial applicationrevealed the treatment area to be completely healed with near completeresolution of the original treated lesion, but for a small area at theinferior edge of the prior application site. The area was again treatedat that time using the method outlined above, with the same procedure,same response, and no complications. Superficial crusting againdeveloped over the treated area, which resolved within “about a week”according to the subject. A follow-up 31 days after the secondapplication revealed complete resolution of the lesion with outstandingcosmesis. The subject was extremely pleased with the results. Along-term follow-up 193 days after the first application (155 days afterthe second application) revealed no recurrence of the original SK lesionand that the outstanding cosmesis was maintained.

Example 19

A vehicle-controlled, within subject study of the bioavailability of ahydrogen peroxide and 2-propanol topical solution administered undermaximal use conditions in subjects with clinically typical seborrheickeratosis on the back will be undertaken. The main objective of thisstudy will be to assess the relative bioavailability of a solution of40% hydrogen peroxide/5% 2-propanol when administered topically underconditions of maximum use in subjects with seborrheic keratosis (SK) onthe trunk, face, and extremities. A further objective will be toevaluate the safety of the 40% hydrogen peroxide/5% 2-propanol solutionwhen administered topically under conditions of maximum use in subjectswith seborrheic keratosis on the trunk, face, and extremities. It isexpected that each subject will have 10 SK target lesions on the trunk,face, and extremities for treatment and evaluation. At least one targetlesion on each subject will be on the face. During this study, theinvestigator will identify 10 eligible SK lesions on each subject'strunk, face, and extremities. Each SK target lesion will be treated once(first) with a solution vehicle to obtain non-treated pharmacokineticblood samples, and then, one week later, with the active formulation.

Blood samples for pharmacokinetic (PK) analysis of hydrogen peroxidewill be collected at time points ranging from 0 hour (just prior to thestudy medication application) to at least about 6 hours after the studymedication application is completed. PK samples will be collected at thesame time of day to eliminate complications associated with anypotential diurnal variation in endogenous hydrogen peroxide plasmalevels. The investigator will measure clinical parameters of the lesionsincluding the lesion dimensions (i.e., length and width) for each targetlesion at Visit 1. A statistical analysis will be performed and relativebioavailability will be calculated for the active solution compared tovehicle solution. The statistical analysis may include an analysis ofvariance (ANOVA) for the PK parameters of Cmax, AUC0-t, and AUC0-∞. Datafor Cmax and AUC0-t will be subject to natural log transformation priorto analysis.

It is anticipated that the main objective of this study will beachieved- to assess the relative bioavailability of a solution of 40%hydrogen peroxide/5% 2-propanol when administered topically underconditions of maximum use in subjects with seborrheic keratosis (SK) onthe trunk, face, and extremities. It is anticipated that no measurableblood level of hydrogen peroxide will be detected under these maximaluse conditions. It is anticipated that the further objective- toevaluate the safety of the 40% hydrogen peroxide/5% 2-propanol solutionwhen administered topically under conditions of maximum use in subjectswith seborrheic keratosis on the trunk, face, and extremities will beachieved. It is anticipated that the test solution will be found to besafe for use when administered topically under these maximal useconditions.

Example 20

An applicator having a topical composition solution having 40% hydrogenperoxide and 5% isopropyl alcohol disposed within a frangible ampouledisposed in the applicator body of the applicator is obtained fortreating a patient having seborrheic keratosis lesions on the face,trunk, and extremities. The lesion is cleansed by rubbing with a 70%isopropyl alcohol wipe, before treatment. The applicator is activated bydepressing the exterior of the applicator body with thumb and forefingerto break the frangible ampule and release the solution. The applicatorshould be held away from the patient while activating the package. Afterthe applicator is activated, the cap is removed, and the tip is wettedby gently squeezing the exterior of the applicator body until thepackage tip is wet with a quantity of solution sufficient to wet thelesion with a thin film.

Using appropriate pressure, the solution is applied to the lesion usinga circular motion for 20 to 30 seconds. During the application, anyexcess solution should be removed from surrounding skin using a cleanabsorbent wipe.

The treated lesion is undisturbed for approximately 1 minute and thenthe application is repeated. This can be repeated up to 4 times untilthe lesion(s) is completely saturated with solution.

After completing treatment of each targeted lesion, the lesion(s) shouldnot be disturbed until the solution has completely dried. The treatedlesions may be dabbed, without wiping, with an absorbent wipe to ensurethe treated lesion is dry before the patient is released.

If the lesion(s) has not completely cleared after approximately threeweeks, further treatment(s) may be applied by following the initialprocedure.

Example 21

An applicator will have an applicator body formed from HDPE, LDPE, or anHDPE/LDPE blend, with a borosilicate glass ampoule arranged therein. Asingle treatment dose of a formulation of 40% w/w hydrogen peroxide and5% 2-propanol will be disposed within the ampoule. An operator will holdthe applicator in their hand in a manner similar to holding a writingutensil to write. The operator will position an index finger on a firstpressure area arranged on an external surface of the applicator body andthe opposing thumb on a second pressure area arranged on a substantiallyopposite side of the applicator body. The operator will squeeze theapplicator body using their index finger and opposing thumb withsufficient force to rupture the ampoule arranged within the applicatorbody between the first pressure area and the second pressure area. Theoperator will shift the position of their hand on the applicator down toa grip area on a proximal portion of the applicator body. The operatorwill cause the formulation to be released from a nylon flocked doe-footshaped tip of the applicator in fluid communication with the applicatortube by squeezing on the grip area using their fingers.

A filter formed from LDPE that is coated with a silicone materialconfigured to impart hydrophobic properties to the filter will bearranged within the applicator to filter the shards from the rupturedampoule. The filter will prevent the flow of the formulationtherethrough unless the operator applies pressure to the applicatorbody. The operator will control a rate of flow from the applicator ontoa target application site (e.g., a skin lesion) by varying the pressureapplied to the grip area. The operator will then treat the target lesionor lesions.

Although the present invention has been described in considerable detailwith reference to certain preferred embodiments thereof, other versionsare possible. Therefore the spirit and scope of the appended claimsshould not be limited to the description and the preferred versionscontained within this specification.

What is claimed is:
 1. An applicator configured to store and dispense atopical composition comprising an agent selected from a caustic agent,an unstable agent or a combination thereof, the applicator comprising: afrangible ampoule having the agent disposed therein, an applicator bodyhaving the frangible ampoule arranged therein; an applicator hub influid communication with the applicator body; a tip arranged at aproximal end of the applicator hub; and a filter arranged between thefrangible ampoule and the tip.
 2. The applicator of claim 1, wherein theagent comprises from about 25% hydrogen peroxide to about 50% hydrogenperoxide.
 3. The applicator of claim 1, wherein the frangible ampoulefurther includes up to 5% 2-propanol.
 4. The applicator of claim 1wherein the applicator body further comprises an additional ingredientof the topical composition disposed therein, whereby the agent isreleased from the frangible ampoule responsive to the frangible ampoulebeing ruptured and is mixed with the additional ingredient in theapplicator body prior to administration of the topical composition. 5.The applicator of claim 1, wherein the topical composition is releasedfrom the frangible ampoule responsive to the frangible ampoule beingruptured and flows through the applicator body, the filter, and out ofthe applicator through the tip.
 6. The applicator of claim 1, furthercomprising a pressure area arranged on an outer surface of theapplicator body to indicate a portion of the applicator body to applypressure to rupture the frangible ampoule.
 7. An applicator configuredto store and dispense a topical composition comprising from about 25% toabout 50% hydrogen peroxide and up to 5% 2-propanol, the applicatorcomprising: a frangible ampoule having the topical composition disposedtherein, an applicator body having the frangible ampoule arrangedtherein; an applicator hub in fluid communication with the applicatorbody; a tip arranged at a proximal end of the applicator body; and afilter arranged between the frangible ampoule and the tip.
 8. Theapplicator of claim 7, wherein the frangible ampoule is formed from atleast one of glass, plastic, borosilicate glass, Type 1 borosilicateglass, and tinted glass.
 9. The applicator of claim 7, wherein theapplicator body is formed from polypropylene, high-density polyethylene,low-density polyethylene, polyvinyl chloride, polyethylene, or acombination thereof.
 10. The applicator of claim 7, wherein the filteris configured to prevent shards of a ruptured frangible ampoule frompassing through and to allow the topical composition to flow through.11. The applicator of claim 7, wherein the filter is formed from atleast one of polypropylene, high-density polyethylene, low-densitypolyethylene, polyethylene, polystyrene, a ceramic material, a foammaterial, sand, diatomaceous earth, and paper fibers.
 12. A method oftreating a skin condition, the method comprising administering a topicalcomposition comprising up to 50% hydrogen peroxide and up to 5%2-propanol using an applicator comprising: a frangible ampoule havingthe topical composition disposed therein, an applicator body having thefrangible ampoule arranged therein; an applicator hub in fluidcommunication with the applicator body; a tip arranged at a proximal endof the applicator hub; and a filter arranged between the frangibleampoule and the tip.
 13. The method of claim 12, wherein the skincondition is selected from the group consisting of warts, seborrheickeratosis, acrochordons, recalcitrant warts, recurrent warts, treatmentnaïve warts, common warts, palmoplantar warts, flat warts,epidermodysplasia verruciformis related warts, anogenital warts,condyloma accuminatum, cervical intraepithelial neoplasia (CIN), chickenpox, Herpes zoster, shingles, molluscum contagiosum, orf, callus,cutaneous horns, corns, fibroepithelial polyps, prurigo nodularis,actinic keratoses, squamous cell carcinoma, squamous cell carcinoma insitu, keratoacanthoma, basal cell carcinoma, cutaneous lymphomas, benignlymphocytic infiltrates, hyperplasias of the skin, clear cell acanthoma,large cell acanthoma, epidermolytic acanthoma, porokeratosis,hyperkeratosis, keratosis pilaris, lichenoid keratosis, acanthosis,acanthosis nigricans, confluent papillomatosis, reticulatedpapillomatosis, nevi, acne, cysts, trichofolliculoma, fibrofolliculoma,perifollicular fibroma, trichodiscoma, nevus sebaceous, chondroidsyringoma, trichoepithelioma, trichoblastoma, desmoplastictrichoepithelioma, pilomatricoma, pilomatrical carcinoma, tricholemmoma,trichelemmal carcinoma, tumor of the follicular infundibulum,tricoadenoma, proliferating pilar tumor, sebaceous hyperplasia,sebaceous adenoma, sebaceous epithelioma, sebaceous carcinoma,syringoma, poroma, hidradenoma, apocrine hidradenoma, spiradenoma,cylindroma, eccrine nevus, papillary adenoma, papillary adenocarcinoma,ephilides, café-au-lait macules, Becker's melanosis, lentigines, solarlentigines, lentigo simplex, mucosal melanocytic lesions, Mongolianspots, Nevus of Ota, blue nevus, common acquired melanocytic nevi,moles, congenital nevi, nevus spilus, recurrent nevi; vascular andperivascular neoplasms, hemangiomas, cherry angiomas, hobnailhemangiomas, tufted angiomas, hemangioendotheliomas, angiolymphoidhyperplasia with eosinophilia (ALHE), glomangiomas, hemangiopericytomas;neuromas, Schwannomas, neurofibromas, nerve sheath tumor, nerve sheathmyxoma, neurothekeoma, granular cell tumor; fibroepithelial polyps,fibromas, fibrous papules, angiofibromas, pearly penile papules,periungual fibromas, dermatofibromas, fibrokeratomas, sclerotic orpleomorphic fibromas, connective tissue nevi, cutaneous scars,hyperplasias, keloids, rosacea, cutaneous fungal, dermatophyteinfections, mold infections, onychomycosis, hyperpigmentation, rhytides,psoriasis, malignant melanoma, dermatosis papulosis nigra, invertedfollicular keratosis, acrokeratosis verruciformis, stucco keratosis, anda combination thereof.
 14. The method of claim 12, wherein the skincondition is selected from the group consisting of warts, common warts,recalcitrant warts, treatment naïve warts, molluscum contagiosum,acrochordons, seborrheic keratosis, condyloma acuminata, or acombination thereof.
 15. The method of claim 12, wherein administeringthe topical composition comprises applying a squeezing force to theexterior surface of the applicator body to dispense the composition. 16.The method of claim 12, wherein administering the topical compositioncomprises contacting the tip with a targeted lesion of the skincondition whereby the topical composition dispenses through the tip ontothe targeted lesion.
 17. The method of claim 12, wherein administeringthe topical composition further comprises applying pressure to apressure area arranged on an outer surface of the applicator bodycausing the frangible ampoule to rupture.
 18. The method of claim 12,wherein administering the topical composition comprises causing thefrangible ampoule to rupture and release the topical composition throughthe tip; and contacting the tip to a targeted lesion of the skincondition.